The European Society
of Human Genetics


ESHG welcomes the Council of Europe’s new protocol on genetic testing

The Council of Europe’s protocol on genetic testing for health purposes* came into force yesterday (Sunday 1 July). The protocol, an addition to the Convention on Human Rights and Biomedicine, lays down rules on the conduct of genetic tests, including direct-to-consumer testing. It specifies the conditions under which tests may be carried out on persons not able to consent, with particular attention to children, and addresses privacy issues and the right to information obtained through genetic testing. It also covers counselling and screening.

The protocol enters into force thanks to its ratification by five Council of Europe member states (Norway, Montenegro, the Republic of Moldova, Slovenia and Portugal). It has also been signed by five others – the Czech Republic, Finland, France, Iceland and Luxembourg. The major push for ratification came from the Czech Presidency of the Council of Europe, following extensive lobbying by the Czech Society of Medical Genetics and Genomics.  “It was a major effort on our part,” says Professor Milan Macek, President of the Czech Society, “and we are delighted by the result.”

“At a time when genetics and genomics are advancing so rapidly, issues surrounding genetic testing take on an even greater importance than before,” says ESHG President Professor Gunnar Houge, University of Bergen, Norway. “New technologies and discoveries provide huge potential for the improvement of human health, but alongside that can go the potential for misuse. The ESHG therefore welcomes the Council of Europe protocol and believes that it will be an important factor in ensuring that genetic progress continues to be applied in the most ethical way possible to the benefit of all concerned.”


Tuuli Lappalainen wins the 2018 Leena Peltonen Prize

The winner of this year’s Leena Peltonen prize, to be awarded at the ESHG annual meeting in Milan, is Dr Tuuli Lappalainen, from Columbia University, New York Genome Center, NY, USA.The prize is awarded to an outstanding young researcher in the field of human genetics.  The prize honours the memory of Dr. Leena Peltonen, a world-renowned human geneticist from Finland who died in 2009, and contributed greatly to the identification of disease genes for human diseases.

After obtaining an MSc in Genetics from the University of Turku, Finland and a PhD atInstitute for Molecular Medicine Finland,University of Helsinki,Finland,Dr Lappalainen pursued her 

career first in Switzerland, and then in the US. Today she is Assistant Professor in the Department of Systems Biology at Columbia, andAssistant Investigator and Core Member at the New York Genome Center. 

Her research focus is onfunctional genetic variation in human populations. She and her research group at NYGC study regulatory variation affecting the transcriptome, as well as cellular mechanisms underlying genetic associations to diseases. The work of her research group links computational and population genomics to experimental molecular biology. She plays a major role in several consortium projects thatproduce essential resources for the human genetics and genomics research community, creating and integrating functional genomics data sets from hundreds or thousands of people. To date, the largest project she has been involved in is the GenotypeTissueExpression(GTEx) Consortium where she has been a key member since 2011. She iscurrentlyco-leadingtheanalysis for the finalmainpaperoftheconsortium, building the largest map in existence of genetic effects on gene expression across dozens of tissues.

“Tuuli’s commitment to international collaboration as well as her philosophy of empowering and inspiring the next generation of genomic researchers mirrors Leena Peltonen’s values and vision for advancing the field,” said a member of the award’s nominating committee, Samuli Ripatti, PhD, Professor of Biometry Public Health, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Broad Institute of MIT and Harvard.

European Human Genetics Conference 2018

June 16-19, 2018, Milan, Italy

Rapid bedside genetic testing can prevent antibiotic-related hearing loss in new-borns treated for sepsis

Milan, Italy:  More than a million neonatal deaths worldwide each year are estimated to be due to sepsis1. In the UK there are approximately 90,000 admissions to neonatal intensive care units per year. Nearly all these patients receive antibiotic therapy during their hospital stay, but babies with a specific genetic change can suffer irreversible hearing loss as a result. Now, in a collaboration between Manchester-based geneticists and a molecular diagnostics company, a rapid test for distinguishing those infants who will have this adverse reaction to the antibiotic gentamicin has been developed. 

Dr John McDermott, from the Manchester Centre for Genomic Medicine, Manchester, UK, will tell the annual conference of the European Society of Human Genetics tomorrow (Saturday) that their simple test for bedside use can produce a result in around 40 minutes. « In the absence of a point of care testing approach we are reliant on core hospital testing facilities, which can take up to three days to provide a result.  This is inadequate, considering that life-saving antibiotics need to be given in the first hour of admission, » he says. « Our test, developed together with a Manchester based company, uses a cheek swab and can allow tailored prescribing.  We are thus able to avoid the antibiotic-related deafness that can occur in infants with this genetic mutation. »

Although there are several antibiotics that can be used to treat sepsis, the UK National Institute for Health and Care Excellence (NICE) recommends a combination of penicillin and gentamicin because the combination has a narrow spectrum of activity and hence a lower risk that the patient might develop antibiotic resistance. But, in new-borns, a particular mutation in mitochondrial DNA2that is present in one in every 500 of the population, means that a single dose of gentamicin can cause profound and irreversible hearing loss.

 “The development of our test has provided us with an exciting opportunity to explore how genetic information can be used in acutely unwell patients, » says Dr McDermott. « As genomic data become ever more prevalent in the population, studies like this will be essential in establishing how patients, clinicians and healthcare systems respond to genetic information being used to personalise treatment as part of everyday healthcare. »

The collaboration plan to undertake a multi-centre feasibility study introducing the test into several neonatal centres around the UK3. All children admitted to these centres will be tested for the genetic change and antibiotics tailored accordingly. « This represents the first example of a point of care genetic test being used in the acute setting, » Dr McDermott will say. « Acute neonatal disease is hugely distressing for all concerned, and we are delighted to be able to contribute to the safety and efficacy of its treatment. »

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University in Newcastle, United Kingdom, said: “This study shows us the importance of rapid genetic tests to prevent severe side effects from the use of antibiotics in a small group of sepsis patients who carry a mutation in their DNA. Identifying those patients within an hour can now allow doctors to prescribe alternative drugs in this group of patients, whereas the majority of patients can safely use the standard antibiotics.” 


Abstract no: C01.3. Development of a point of care pharmacogenetic test to avoid antibiotic related hearing loss in neonates
Session C01 - Precision and Predictive Medicine, Saturday, June 15, 16:00 - 18:30 hrs

1 Sepsis, also referred to as blood poisoning or septicaemia, is a potentially life-threatening condition, triggered by an infection such as pneumonia or a urinary tract infection. In neonates the symptoms of sepsis can include extreme tiredness, mottling of the skin and an abnormally fast breathing rate. It is essential that treatment is started as quickly as possible. 

2 DNA found in the mitochondria (organelles within a cell that convert chemical energy from food into a form that cells can use) makes up a small proportion of the total DNA found in cells.  It encodes for a very small number of genes and is inherited solely from the mother. 

3 The initial study will take place in two large neonatal units in Manchester and Liverpool, and will expand nationwide at a later date.

The research was funded by Action on Hearing Loss.

New technique provides accurate dating of ancient skeletons

Milan, Italy:  Interest in the origins of human populations and their migration routes has increased greatly in recent years. A critical aspect of tracing migration events is dating them. However, the radiocarbon techniques*, that are commonly used to date and analyse DNA from ancient skeletons can be inaccurate and not always possible to apply. Inspired by the Geographic Population Structure model that can track mutations in DNA that are associated with geography, researchers have developed a new analytic method, the Time Population Structure (TPS), that uses mutations to predict time in order to date the ancient DNA.

Dr Umberto Esposito, a postdoctoral research in the laboratory of Dr Eran Elhaik, Department of Animal and Plant Sciences at the University of Sheffield, Sheffield, UK, will tell the annual conference of the European Society of Human Genetics today (Monday) that TPS can calculate the mixtures of DNA deriving from different time periods to estimate its definitive age. “This introduces a completely new approach to dating.  At this point, in its embryonic state, TPS has already shown that its results are very similar to those obtained with traditional radiocarbon dating. We found that the average difference between our age predictions on samples that existed up to 45,000 years ago, and those given by radiocarbon dating, was 800 years. This study adds a powerful instrument to the growing toolkit of paleogeneticists that can contribute to our understanding of ancient cultures, most of which are currently known from archaeology and ancient literature,” says Dr Esposito.

Radiocarbon technology requires certain levels of radiocarbon on the skeleton, and this is not always available. In addition, it is a delicate procedure that can yield very different dates if done incorrectly. The new technique provides results similar to those obtained by radiocarbon dating, but using a completely new DNA-based approach that can complement radiocarbon dating or be used when radiocarbon dating is unreliable.

 « This permits us to open a powerful window on our past. The study of genetic data allows us to uncover long-lasting questions about migrations and population mixing in the past. In this context, dating ancient skeletons is of key importance for obtaining reliable and accurate results, » says Dr Esposito. « Through this work, together with other projects that we are working on in the lab, we will be able to achieve a better understanding of the historical developments that took place from the beginning of the Neolithic period, with the introduction of farming practices in Europe, and throughout the Bronze and Iron Ages. These periods include some of the most crucial events involving the population movements and replacements that shaped our world. »

The technique is also expected to be valuable for genealogy. « When applying our ancient DNA dating technology to modern genomes, we have seen that some populations have more ancient genomes than others, and this can be helpful in establishing individual origins » says Dr Esposito.

Health research will benefit too. Since the study of genetic disorders is closely tied up with questions of ancestry and population stratification, being able to analyse the homogeneity of populations is of vital importance to epidemiologists.

The researchers are currently compiling a larger dataset to increase the geographical/time coverage of their model and improve its accuracy. « Given the rapid increase in the number of ancient skeletons with published DNA, we believe that our technique will be useful to develop alternative hypotheses,» Dr Esposito will say.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University in Newcastle, United Kingdom, said: “This study shows how DNA derived from ancient skeletons can be used to more accurately determine the age of the skeleton than traditional radiocarbon tracing methods. This is another example of the power of modern genomics technologies to assist in helping us understand where we come from, how the journeys of our forefathers have helped shape our current genome and how this now impacts our current abilities and weaknesses, including risks of disease.”


*Radiocarbon dating is a method for determining the age of an object by analysing the amount of radioactive carbon dioxide it contains. When an animal or plant dies, it stops exchanging carbon with its environment, and measuring the amount that remains provides a method of determining when it died.

Abstract no: C16.4 Time informative markers to date ancient skeletons
Session C16. Multi-Omics 2, Monday, June 17, 2018, 13:00 - 14:30 hrs

The research was funded by the UK Engineering and Physical Sciences Research Council and the DNA Diagnostics Centre (DDC).

Genomic testing for the causes of stillbirth, fœtal congenital abnormalities and neonatal death can provide hard-to-get answers and should be considered for routine use

Milan, Italy:  Pregnancy loss and the death of a newborn baby are devastating events, and as of today around 25% of these perinatal deaths are unexplained despite autopsy. Discovering the cause of such a loss is of great importance for the bereaved parents, both in providing an explanation and in helping them to understand the likelihood of a recurrence in future pregnancies. Researchers in Australia have used state of the art genetic testing in order to to help provide answers in such cases.

Associate Professor Christopher Barnett, a clinical geneticist who is Head of the Paediatric and Reproductive Genetics Unit at the Women’s and Children’s Hospital, North Adelaide, will tell the European Society of Human Genetics conference today (Monday) how he and colleagues are using whole exome sequencing (WES)1 and whole genome sequencing (WGS)2 to detect causes of neonatal death in cases where this has so far remained unidentified. Using data from 43 families referred to the genetics unit, where samples were available from both parents and the fœtus (the prospective cohort), and 60 from stored autopsy samples from the fœtus or newborn (the retrospective cohort), the researchers were able to uncover an underlying genetic cause in 23% of the prospective cohort, and have found a single promising candidate in a further 26%.

Solved cases included new disease gene discoveries, new syndrome identification and novel severe fœtal presentations of existing rare paediatric disease. In the retrospective cohort, strong candidates for the cause of death were found in 18% of cases.

« This study has contributed directly to the birth of healthy babies, » Prof Barnett will tell the conference. « We have had numerous couples who, with successful preimplantation genetic diagnosis via in vitro fertilisation in subsequent pregnancies, or through prenatal testing during pregnancy, have been able to avoid the genetic condition experienced in a prior pregnancy. Of course, this can only be offered to couples if a definitive genetic diagnosis is made in the earlier affected pregnancy, and this is the primary aim of our study. These conditions are often extremely rare and, indeed, in some cases they are totally new. »

According to the World Health Organisation, in 2009 there were 2.6 millions stillbirths (the death of the fœtus at or after 22 weeks of pregnancy) across the world, with more than 8200 deaths per day. Among the 133 million babies born alive each year, 2.8 million die in the first week of life.

In Australia, a standard perinatal autopsy is done in about 60% of cases of unexplained fœtal or neonatal death and termination of pregnancy for congenital abnormalities. Some genetic testing is done, but it is limited, usually to chromosomal analysis. As in most other countries, specific genetic sequencing is not a standard part of the autopsy process and when it does occur it is generally limited to a particular condition or a relatively short list of genes. « We are offering the testing of all human genes so that we can increase the rate of diagnosis as much as possible,» says Prof Barnett.

One of the main ethical features of the study is that it involves testing the parents as well as the fœtus/newborn. This means that the consent procedure needs to be rigorous, and occur in a face to face setting with the clinical geneticist at the time of the counselling that is provided for follow-up of the first autopsy. The genetic diagnoses of the parents may have the potential to affect their health later in life, and the consent process allows them to opt out from knowing these results if they so wish.

« Our results provide new insights into the molecular mechanisms of early development. We are not surprised that a significant proportion of ‘unexplained’ fœtal and newborn deaths and congenital abnormalities have an underlying genetic cause, and we believe that genomic autopsy should be used routinely in the investigation of pregnancy loss and perinatal death, » Prof Barnett will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University in Newcastle, United Kingdom, said: “It is often unclear what the cause is of pregnancy loss or the death of a newborn baby. This work shows how state-of-the-art genomic testing can be used as part of the routine autopsy procedure to reveal a genetic cause in up to a quarter of all neonatal cases. A genetic diagnosis can be used to prevent complications in future pregnancies and provide much needed answers to the families involved.”


1.Whole exome sequencing is a technique for sequencing all the genes in a genome that code for proteins. Because disease-causing genes are much more likely to be found in the protein-coding sequence, focusing on this limited area costs much less than whole genome sequencing but is still able to provide a high yield of results.

2. Whole genome sequencing is the process of determining the complete DNA sequence of an individual, including all the chromosomal DNA and that contained in the mitochondria.

Abstract no: C15.5. The Genomic Autopsy Study: using genomics as an adjunct to standard autopsy to unlock the cause of complex fetal and neonatal presentations
Session C15 Syndrome Updates 2, Monday, June 18, 2018, 13:00 - 14:30 hrs

The research was funded by the Australian National Health and Medical Research Council (NHMRC), and sequencing support provided by the Broad Institute in Boston, USA.

Individual access to genomic disease risk factors has a beneficial impact on lifestyles

Milan, Italy:  Giving personal genomic information to individuals can have a major, long-term effect on their lifestyle, researchers have found. The Finnish GeneRISK study, providing information on the risk of cardiovascular disease (CVD) based on their genome and traditional risk factors to 7,328 people inspired changes for the better in areas such as weight loss and smoking cessation. Nearly 90% of them said the information had made them take better care of their health, the annual conference of the European Society of Human Genetics will hear today (Saturday).

Although there is plenty of evidence that genomic factors have an important impact on the risk of common diseases, to date there has been little use of this information in prevention. Elisabeth Widen, MD, a senior scientist at the Institute for Molecular Medicine, University of Helsinki, Finland, and colleagues have developed a web-based tool that allows patients and doctors to see and manage genomic information based on 49,000 disease-associated genetic variants and lifestyle-associated risk factors.

« Delivering the results of the tool KardioKompassi® directly to patients, they were able to see their 10-year risk for ischemic heart disease. The tool combines risk information based on traditional risk factors such as age, sex, cholesterol levels and blood pressure with a polygenic risk score. Where a patient’s overall disease risk was elevated, KardioKompassi advised the participant to contact their doctor in order to discuss how best to reduce it, » Dr Widen will say.

When reassessed eighteen months later, the results were impressive. Compared with a 4% smoking cessation rate in the general population, 17% of smokers in the study had given up, and sustained weight loss had been achieved by 13.7% of participants. Overall, risk-reducing behaviour such as weight loss, giving up smoking, or visiting a doctor was 32.4% in those with a predicted CVD risk of more than 10% and 18.4% in those at lower risk.

« As many as 40% of participants with a high risk of CVD were smokers at the start of the study, so these results are encouraging. We believe that giving information on their genetic profile to individuals is particularly motivating, perhaps simply because it is new information. For example, many of the participants already knew that they had high levels of cholesterol. But it was receiving information on their personal genetic risk that triggered changes, » Dr Widen says.

GeneRISK participants will be recalled for follow-up studies over the next 20 years and their health status will be closely followed. The researchers believe that those who have already made lifestyle changes are likely to continue them. « Since they have managed to maintain these changes for 1.5 years, we expect them to persist, » says Dr Widen.

The general trend towards patient participation is particularly important in disease prevention, say the researchers. Empowering individuals by giving information on their personal risk of disease, as opposed to something more generalised, is clearly effective in encouraging them to follow healthier lifestyles.

« Our results show that this approach to managing and interpreting genomic data for individuals is feasible and effective. We think that our study provides a model for the use of such data in healthcare that can be easily adapted to other diseases, where we believe that it is likely to be equally valuable, » Dr Widen will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “It is impressive to see how genomic information can be used successfully to promote a healthier lifestyle in people at higher risk of developing heart disease. Clearly in the population there will also be many people with a relatively lower genetic risk of developing common diseases, and I do wonder what would happen if these people are informed about this; would they start showing an unhealthier lifestyle? This field of predictive genomic medicine is only just emerging, with lots of opportunities for further research.”


Abstract no: C01.2 Returning cardiovascular disease risk prediction back to individuals motivates beneficial lifestyle changes : Preliminary results from the GeneRISK study
Session C01 - Precision and Predictive Medicine, Saturday, June 15, 16:00 - 18:30 hrs

The research was funded by Business Finland with support from the University of Helsinki, Carea - Kymenlaakso social and health care services, Kotka, Finland, Mehiläinen Oy, Helsinki, Finland, and the Finnish Red Cross Blood Service.

Whole Genome Sequencing helps diagnosis and reduces healthcare costs for neonates in intensive care

Milan, Italy:  Children who are born severely ill or who develop serious illness in the first few weeks of life are often difficult to diagnose, with considerable implications for their short and longer-term care. Whole genome sequencing*carried out quickly has the potential to provide an early diagnosis, and thus improve the clinical care of these infants as well as reducing its cost, the annual conference of the European Society of Human Genetics will hear tomorrow (Sunday).

Dr Shareef A. Nahas, Senior Director, Rady Children’s Institute for Genomic Medicine, San Diego, CA, United States, will report on his team’s study of rapid whole genome sequencing (rWGS) of all inpatient children under one year of age who were nominated for genetic investigation at Rady Children’s Hospital. Rapid WGS is able to return results in 48 to 96 hours, whereas standard genetic testing takes six to eight weeks to provide a result. They then noted subsequent changes in medical care that occurred while the child was still in hospital. Where there was a significant change in care due to a new diagnosis, the cases were reviewed by an independent expert panel who tried to determine what they believed would have happened had the child not received rWGS.

After 12 months of testing, 363 patients had been enrolled in the study and rWGS interpreted in 340 of them.  This yielded a diagnosis in 115 cases (about 34%). Diagnosis occurred quickly, on average within 96 hours. Changes in management as a result of diagnosis were identified in 77 patients, or about 67% of those diagnosed. Such changes ranged from specific changes, for example surgical interventions, to guidance in palliative care. Among the first 42 infants diagnosed, rWGS provided over $1.3million in net cost saving over the projected standard care.

“To date, our studies have shown a considerable clinical and economic benefit of sequencing children who were identified by clinicians as being suspected of having a genetic disorder.  In the course of the study, one child was spared devastating neurological damage,and one had a significantly reduced risk of death. The net cost savings totalled several hundred thousand dollars, even when we included the cost of analysing the genome of the child and both parents, » says Dr Nahas. 


Although many studies have shown that WGS improves the diagnosis if genetic disorders in infants and can lead to beneficial changes in their management, the new research has shown that, by implementing rapid sequencing, cost savings will also ensue.« We are now in a situation where we have a technology that leads to improved diagnosis and improved outcomes but is also not a net burden on healthcare resources. This means that for large healthcare payers, there is not a logical cost barrier to implementing rWGS in neonates suspected to have a genetic disorder. There will need to be further data on who else can benefit from early use of this technology  but implementation in the current cohort should not be delayed, » says Dr Nahas.


Currently, the use of WGS among sick neonates is very infrequent across the world, and there are few healthcare systems that have the ability to turn round genetic testing quickly enough to be clinically relevant, the researchers say. This is vital if medical management needs to be changed during the childrens’ hospitalisation. In the course of Dr Nahas’ study, one child was spared devastating neurological damage and another had a significantly reduced risk of death.


« The logic for the use of rWGS in these patients, both diagnostic and economic, is totally convincing. We have demonstrated that early sequencing saves money during admission. We were surprised by the proportion of children who received a change in care during that admission – around 25% of children sequenced and 80% of those diagnosed. This rate is much higher than other published rates for neonates who received WGS. We believe that this difference is due to the fact that the children received results at a much younger age, at a point where medical decisions were yet to be made.


 « There is an ethical imperative to act in the best interest of neonates, but implentation will require a concerted effort across all healthcare systems, and this will need to be at government level in Europe. Consistent with many diagnostic tests in the post-natal period, rWGS has the potential to identify conditions associated with lifelong disability or shortened lifespans, » Dr Nahas will conclude.


In a second presentation, Courtney French, PhD, a research associate/bioinformatician at the University of Cambridge, Cambridge, UK, will describe how she and colleagues carried out WGS analyses on 145 severely ill babies and children with an unidentifiable disease.  As a result, they were able to identify the cause of disease in more than 15% of cases.

« We have developed a rapid, affordable turnaround pipeline for this sequencing within the UK National Health Service system. This means that we can feed back clinically relevant information to doctors and parents in a timescale that allows care to be affected. Because it is hard to tell from observation alone who will benefit from genomic diagnosis, we think that it should be carried out on all eligible children, rather than doctors deciding on individual cases based on previous clinical knowledge. By comparing the entire DNA sequence in children to that of their parents we can identify quickly the likely cause of disease, » says Dr French.

The researchers are using their current data to investigate how rare genetic diseases present at an earlier stage than they are usually diagnosed in newborns. « Greater numbers of patients will expand our ability to do this, and we hope that our work will serve as a model for expanding the programme to other hospitals and regions, » Dr French will say. « The success of this project will depend on people working together across the health research and healthcare system. The translation of this work to routine care will require significant investment of resources in achieving consent from parents, and in giving information at what is a very stressful time for them. »

Many of the conditions characterised through WGS to date can be treated more effectively once identified. In the Cambridge dataset, several epilepsies that respond better to some medications than others were found. And there were cases where the diagnosis was able to prompt better screening for the clinical consequences of a condition and enabled the creation of a properly focused care plan, for example cardiac surveillance, renal follow up, or dietary advice. Even where there is no effective treatment available, having a diagnosis can provide reassurance to families that all that could be done has been done, and it can also provide useful information to parents when they are considering the most appropriate care for their child in the future.

« We were pleasantly surprised at the enthusiastic welcome parents gave to our study, with more than half of those approached wanting to take part. Despite the complications of getting samples from both parents, as well as their child, we managed to achieve this in 85% of families. We were also surprised at the huge range of clinical conditions we were able to diagnose, and particularly to find that when a child was already known to have learnng disability or developmental delay we were more likely to make a genetic diagnosis. This reflects the enormous increase in genetic knowledge over the last decade; ten years ago we would not have been able to do this even if we had sequenced the genome.

« Genome sequencing is currently rare in newborns and paediatric cases, but our research has shown that it can be extremely effective in providing rapid answers in difficult to diagnose cases. It is also be cost-effective, since it can reduce the time spent as an in-patient. Early diagnosis of neonatal and paediatric disease is not only important in pointing the way to the best care and treatment, but also in reducing anxiety for parents, » Dr French will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “Both these studies confirm the value of genome sequencing to detect the cause of unexplained disease. The study of Nahas shows that this can now even be done within four days, which is very impressive. This greatly increases the practical use of genetics in an acute clinical setting where treatment decisions can now be made based upon this powerful test. Personalised genomic medicine is becoming a reality!”


*. Whole genome sequencing is the process of determining the complete DNA sequence of an individual, including all the chromosomal DNA and that contained in the mitochondria.

Nahas: Abstract no: CO7.5. Rapid Whole Genome Sequencing Improves Clinical Utility and Cost Effectiveness of Acutely Ill Children admitted to Neonatal Intensive Care Units
Session C07. NGS Doagnostics, Sunday, June 17, 13:00 - 14:30 hrs

The research was funded by the US National Institutes of Health and the Rady Family Foundation

French:Abstract no: CO7.4 Next Generation Children Project: Whole genome sequencing for rapid diagnosis of severely ill children in intensive care

The research was funded by Rosetrees Trust and NIHR BioResource and Cambridge Biomedical Research Centre.


Increasing the age limit for Lynch syndrome genetic testing may save lives

Copenhagen, Denmark:  Raising the age limit for routine genetic testing in colorectal cancer could  identify more cases of families affected by Lynch syndrome, a condition that accounts for around 5% of all colon cancers, according to new research to be presented at the annual conference of the European Society of Human Genetics today (Monday).  Professor Nicoline Hoogerbrugge, head of the Radboud university medical centre expert centre on hereditary cancers, Nijmegen, The Netherlands, will tell the conference that there is an urgent need to find families carrying a mutation for Lynch syndrome in order to decrease mortality from the disease.

“We know that, at present, only between 20% and 30% of people with Lynch syndrome have been identified. Most countries rely on detection through family history and early age at diagnosis, and this leads to significant underdiagnosis. We have shown that, by raising the age limit for testing we are able to detect new affected families who would not have been identified previously,” she says.

The researchers studied results of mismatch repair (MMR) testing in patients up to 70 years of age with colorectal cancer from 14 pathology laboratories. Previously, in The Netherlands, such testing was carried routinely in patients who were aged up to 50. Of 87 patients whose results suggested that they are at high risk of Lynch syndrome, 35 were referred for genetic counselling.

After further testing, Lynch syndrome mutations were definitely identified in 13 of 32 patients with complete genetic testing, and 11 of these patients came from families in which the disease had previously not been detected. Eight of them were aged between 50 and 70 and did not comply with previous referral criteria for genetic testing based on age and family history.

“If we had not studied these older patients, their family predisposition to Lynch syndrome would not have been detected until it was too late,” says Prof Hoogerbrugge. “In every affected family, we can find an average of three people with Lynch. This is clearly a massive advance in the identification of people at risk.”

By implementing appropriate prevention measures, deaths from Lynch syndrome in affected families can be reduced by more than 60% over 15 years, the researchers say. The disease, otherwise known as hereditary nonpolyposis colorectal cancer (HNPCC), also leads to an increased risk of cancers of the stomach, upper urinary tract, brain, skin and prostate, with women carriers at an additional of endometrial and ovarian cancers.

The study covered 20% of the Dutch population. “Part of our results surprised us; we had not expected to find so many mutations in Lynch syndrome associated genes with a relatively high risk of developing tumours in patients without a family history of the disease. This has only strengthened our desire to see an increase in the age limit for MMR testing applied across The Netherlands, and indeed across Europe, so that every new colorectal cancer patient aged below 70 can benefit from it,” says Prof Hoogerbrugge.

“The age limit in the UK has recently been increased; although it is too early to be able to see signs of value there, we have been able to provide clear evidence of its advantages in The Netherlands, both for patients and for health services,” she concludes.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “It is very important to recognise whether a person suffers from sporadic or familiar cancer, as this identifies family members at risk who can take preventative measures. For this, genetic tests need to be done in cancer patients. This study shows that we should extend these genetic tests to older colorectal cancer patients of whom a significant number suffer from familiar cancer.”


Abstract no:  C17.6

The research was funded by the Dutch Maag-Lever-Darm society and the Vriendenloterij.

The data have been updated since submission of the abstract, which accounts for the difference in numbers.

European Human Genetics Conference 2017, May 27-30, Copenhagen, Denmark

China’s mass collection of human DNA without informed consent is contrary to the right to privacy

China holds the largest searchable DNA database in the world; genetic information from over 40 million individuals that is ostensibly to be used in the fight against crime. However, the way in which these data are collected and the protection given to providers leave much to be desired, according to the European Society of Human Genetics (ESHG).

"There is growing evidence that DNA is being collected from ordinary individuals who have not been convicted nor even suspected of a crime, and that this collection is compulsory. Police have also taken samples from groups that are already under increased government surveillance, such as dissidents, migrant workers, and ethnic minorities," said Professor Martina Cornel, chair of the ESHG Public and Professional Policy Committee, today [date]. "Because police powers in China are so extensive and people have little right to privacy, they are unable to refuse to provide such personal data."

People who have been compelled to provide DNA have reported their experiences via social media. Collections are made by police at their workplaces, homes, and schools, with no prior notice and without the presentation of any official document justifying the taking of samples.  Some people have also been asked to provide DNA samples when applying for documents such as residency permits from the police.

In Xinjiang, a province that is home to around 10 million Muslim Uyghurs, an ethnic group already suffering state repression, all passport applicants are now required to provide DNA samples, irrespective of whether or not they are suspects in a criminal case. "This is in total contradiction to all existing regulations and safeguards concerning the collection of DNA samples from individuals", says Prof Cornel.

"We know that such databases can be used for government surveillance, including identification of relatives. Collection of DNA without the subject’s full, informed consent can only be justified in extremely limited circumstances, for example in order to solve a very serious crime. A collection of samples from individuals where no such consent has been given has been ruled illegal by many international bodies, and the very existence of such a database is dangerous."

"ESHG calls on the Chinese government to follow in the footsteps of all responsible authorities and ensure that human DNA is collected only from individuals suspected of having committed serious crimes, and that informed consent is given whenever possible."

New genomic analysis promises benefit in female urinary incontinence

Copenhagen, Denmark:  Urinary incontinence in women is common, with almost 50% of adult women experiencing leakage at least occasionally.  Genetic or heritable factors are known to contribute to half of all cases, but until now studies had failed to identify the genetic variants associated with the condition.  Speaking at the annual conference of the European Society of Human Genetics today (Monday), Dr Rufus Cartwright, MD, a visiting researcher in the Department of Epidemiology and Biostatistics, Imperial College, London, UK, will say that his team’s investigations hold out the promise that drugs already used for the treatment of other conditions can help affected women combat this distressing problem.  

Pelvic floor disorders, including urinary incontinence, but also faecal incontinence and pelvic organ prolapse, have a devastating effect on quality of life. Most commonly they occur after childbirth, or at menopause, though some women report incontinence dating from childhood. Of the 25% who are affected sufficiently for it to affect their daily lives, most suffer from stress incontinence – the loss of small amounts of urine associated with laughing, coughing, sneezing, exercising or other movements that increase pressure on the bladder. Isolated urgency incontinence – where a sudden pressing need to urinate causes the leakage of urine – affects only around 5% of women, and 5-10% have a combination of both forms.

“25% of adult women will experience incontinence severe enough to impact on their quality of life,” says Dr Cartwright. “Finding a genetic cause and a potential treatment route is therefore a priority.”

The researchers undertook a genome-wide association study (GWAS) in just under 9,000 women from three groups in Finland and the UK, confirming their findings in six further studies. Genome-wide association studies work by scanning markers across the complete sets of DNA of large numbers of people in order to find genetic variants associated with a particular disease.

Analysis of the study data yielded a risk locus for urinary incontinence close to the endothelin gene, known to be involved in the ability of the bladder to contract. Drugs that work on the endothelin pathway are already used in the treatment of pulmonary hypertension and Raynaud’s syndrome, a condition where spasm of the arteries causes reduced blood flow, most usually to the fingers.       

“Previous studies had failed to confirm any genetic causes for incontinence. Although I was always hopeful that we would find something significant, there were major challenges involved in finding enough women to participate, and then collecting the information about incontinence.  It has taken more than five years of work, and has only been possible thanks to the existence of high quality cohort studies with participants who were keen to help,” says Dr Cartwright.

Current treatment for urinary incontinence in women includes pelvic floor and bladder training, advice on lifestyle changes (for example, reducing fluid intake and losing weight), drugs to reduce bladder contraction, and surgery.

However, as the number of identified risk variants for urinary incontinence grows, there will be potential to introduce genetic screening for the condition, and improve advice to pregnant women about the likely risks of incontinence in order that they may make an informed choice about delivery method. “We know that a caesarean section offers substantial protection from incontinence. However, across Europe there are efforts to reduce caesarean section rates, and establishing such a screening programme during pregnancy may run against current political objectives in many maternity care systems.

“Clearly this will need further debate and an analysis, not just of the cost to healthcare systems, but also of the benefit to women who may be spared the distress of urinary incontinence,” Dr Cartwright will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “This work reveals the first links between urinary incontinence and genetic factors. It provides important insight into the biological mechanisms for incontinence and suggests the potential of identifying women at risk.”


Abstract no:  C18.4.

The research was mainly funded by the UK Medical Research Council, with additional grants from the International Continence Society and the International Urogynecological Association.

Genomics tracks migration from lost empires to modern cities

Copenhagen, Denmark:  New genomic tools are enabling researchers to overturn long-held beliefs about the origins of populations, a researcher will tell the annual conference of the European Society of Human Genetics today (Monday).  Dr Eran Elhaik, Assistant Professor of Animal and Plant Sciences at the University of Sheffield, Sheffield, UK, will say that new technologies are enabling scientists to track the origins and migrations of populations with increasing accuracy.

Until recently, assumptions about origins were based on where people were buried. “However, this does not take into account the migrations which we now know took place thousands of years ago,” says Dr Elhaik, who carried out the research with colleagues including Dr Umberto Esposito.

Using a recently-developed technology, the ancient Geographic Population Structure (aGPS) tool, the researchers were able to find the geographical origins of ancient DNA, with the only limitation being the availability of DNA data. This in turn enabled them to combine hundreds of snap shots from the past into a reconstruction of modern history from 12,000 BC to the modern era. “This is by far the most comprehensive reconstruction of our genetic history. Our work reveals the colonisation of Europe, step by step, and answers many questions concerning the origins and migrations of Europeans,” says Dr Elhaik.

Applied to a dataset of over 300 ancient Eurasians and Near-Easterners during the Ice Age to Late Iron Age period, aGPS localised around 50% of the samples at up to 200km from their burial site, about 32% at between 200 and 1000km, and the remainder at between 1000 and 3,175km. “The migration patterns revealed by our work were remarkably complex and dynamic, and the difficulties in interpreting them correctly are significant.

“The challenge for us now is to understand why these migrations took place. What caused a particular group of people to make a journey of over 3000km at a time when travel was complicated and dangerous? When we combine our results with archaeological and climate data, we can begin to see why,” says Dr Elhaik. “For example, we can identify areas where the land became exhausted from over-farming, and thus caused the movement of populations. We can also pinpoint the formation of city states and ‘biodiversity centres’, corresponding to ancient empires that drew immigrants from other countries.”

The results allow the researchers to confirm the theory of the massive migration of populations from the steppes of the Caucasus (the Yamnaya) to Central Europe during the Late Neolithic period (3500 to 2300 BC).  “We discovered that Central Europeans were always on the move, continuously mixing with other populations and forming ancient cities in Germany, Denmark and Hungary, for example close to modern-day Hamburg and Berlin, and Budapest. In contrast, Near Eastern peoples tended to stay close to home,” says Dr Elhaik.

“Genetic data can answer many questions that archaeology alone cannot. For example, is a specific decoration indicative of an alien culture, or simply an import? These new insights are fascinating, not just in a historical context, but because they provide additional proof of the unlikelihood of a ‘day zero’ of ethnic homogeneity, except perhaps in a very few isolated places. Even if it had existed, there must be practically no-one alive on earth who could trace all their ancestors to one ethnically homogenous population”.

There are endless challenges in this research. “Imagine working with a very short DNA sequences with more holes than bases – not only can we not align this with other ancient sequences, but we also do not know where it is from. And this is before we get to the question of “when?” which is, again, linked to “where?” because different regions entered developmental periods, like the Iron Age, at different times.

“However, our findings to date have already brought about a far greater understanding of the identity of Old World residents, and our goal is now to reconstruct the full “Human Atlas” showing ancient migration patterns worldwide,” he will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “This fascinating work illustrates the power of modern genetic approaches to study human history and migration. The scientists demonstrate that information in ancient DNA samples, even of low quality, can be used to provide a very precise geographical localisation of the origin of a person.”


Abstract no:  C14.6

The research was partly funded by the DNA Diagnostics Centre, UK.

Obesity can cause cardiovascular ill-health, even in the young

Copenhagen, Denmark:  Higher than normal body mass index (BMI) is known to lead to  cardiovascular ill-health in mid-to-late life, but there has been limited investigation of its effect in young, apparently healthy, adults. Researchers have now shown that having a higher BMI can cause worse cardiovascular health in those aged as young as 17, according to a study to be presented to the annual conference of the European Society of Human Genetics today (Sunday).  

Dr Kaitlin Wade, a Research Associate at the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) at the University of Bristol, Bristol, UK, and colleagues used data from The Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate the potential link between increased BMI and cardiovascular health.  “ALSPAC is a world-leading birth cohort study, started in the early 1990s with the inclusion of more than 14,000 pregnant mothers and their partners and children, and provides an excellent opportunity to study environmental and genetic contributions to a person’s health and development. It was therefore ideal for this purpose,” Dr Wade will say.

The researchers hypothesised that cardiovascular risk due to increased BMI was likely to emerge in earlier life. The design of existing observational studies (those just looking for associations in the population) have meant that they are unable to make a distinction between correlation and causation. The MRC-IEU specialises in the use of genetics to help these difficult analytical situations and in this case researchers were able to use genomic data from ALSPAC to detect the likely causal relationship between higher BMI and higher blood pressure and left ventricular mass index (LVMI) in those aged 17 and 21. A thickening of the left ventricle in the heart (hypertrophy) means that it has to work harder to pump blood and is a common marker for heart disease.

Higher BMI did not appear to have an effect on heart rate in these young adults, although previous studies have shown an association - most likely due to bias caused by the mixing of effects of an additional factor resulting in a distortion of the true relationship (confounding). “Our results showed that the causal impact of higher BMI on cardiac output was solely driven by the volume of blood pumped by the left ventricle (stroke volume). This, at least in part, can explain the causal effect of higher BMI on cardiac hypertrophy and higher blood pressure that we observed in all our analyses,” says Dr Wade.

The results support efforts to tackle the obesity epidemic from an early age in order to prevent the development of cardiovascular changes known to be precursors of cardiovascular ill-health and disease. “It is the first time that the nature of this relationship has been shown in group of young adults where it has been possible to draw improved conclusions about its causation," says Dr Wade.

The researchers are now trying to untangle the relationship between higher BMI and disease mechanisms including metabolomics (the study of the chemical processes involved in the functioning of cells and the abundance and diversity of microbes living in the gut - the gut microbiome). “We have also begun an analysis of the causal role of higher BMI on detailed measures of cardiac structure and function within the ALSPAC data.  We hope to further explore these associations within an older population - the UK 1946 birth cohort.

“Whilst randomised controlled trials are important for disentangling cause and effect in disease, they are expensive, time-consuming and labour-intensive. Modern genomics allows us to detect causality more quickly and cheaply, and the availability of large quantities of genetic data means that we can overcome the limitations of observational epidemiological studies. We believe that there are clear messages for cardiovascular health in our findings and we hope that they may lead to increased efforts to tackle obesity from early life,” Dr Wade will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University¸ Newcastle, United Kingdom, said: “Distinguishing between correlation and causation is tremendously difficult in medical sciences, especially for complex interactions like those between obesity and cardiovascular disease. In this study, statistical genetics approaches were applied to longitudinal cohorts from the UK to improve this. The scientists could demonstrate that obesity also causes poorer cardiovascular health in young adults. In contrast, higher BMI did not seem affect heart rate in this group.’’


Abstract no:  C10.3

The research was funded by the British Heart Foundation, the UK Medical Research Council, The University of Bristol and The Wellcome Trust.

Open-access genetic screening for hereditary breast cancer is feasible and effective

Copenhagen, Denmark:  Ashkenazi Jewish women are known to have a predisposition to the inherited breast cancers BRCA1 and BRCA2, but currently genetic testing in this group is limited to women affected by breast and ovarian cancers and those who are unaffected but have a family history of the disease.

Ms Sari Lieberman, a genetic counsellor at the Shaare Zedek Medical Centre, Jerusalem, Israel, will tell the annual conference of the European Society of Human Genetics tomorrow (Sunday) that offering open-access BRCA testing to Ashkenazi women unaffected by cancer, regardless of their family history, enables the identification of carriers who would otherwise have been missed. Carrying one of the mutations for the BRCA genes means that women affected have a 50-80% risk of developing breast cancer and a 20-50% risk for ovarian cancer.

“We knew that half of these carriers have no family history of cancer, and therefore would not have been identified had the test been offered on the current personal and family history criteria,” she says. “As a genetic counsellor, it is frustrating and saddening to see the results of this policy, where patients are often only identified as BRCA carriers once they have been diagnosed with cancer.”

The researchers streamlined the pre-test process so that traditional genetic counselling, which can be time-consuming and difficult, was excluded. Instead they provided written information about the BRCA genes, the genetic test, and about the implications of being a carrier.

“Current strategies for testing focus on women who are 50 and older, which is not the optimal age for effective prevention. In order to address this, we would like to continue this study and look for other approaches that could include younger women,” says Ms Lieberman.

participants in the study either referred themselves or were recruited by health professionals. Two-year follow up of the 1771 women tested included looking at psychosocial outcomes and health behaviours. Both groups reported a high level of satisfaction (94%) and low stress. Those who had referred themselves tended to be more knowledgeable about breast cancer issues than those who were recruited.

“Among the 25 women carriers we identified, 94% expressed satisfaction and 92% endorsed the idea of population screening. Their stress was understandably higher, but it declined over time, and their knowledge was greater than in non-carriers. All of them had breast surveillance, and three underwent risk-reducing bilateral mastectomy. Of those aged over 40, fifteen out of a total of 16 had their ovaries and Fallopian tubes removed in order to reduce risk,” Ms Lieberman reports.

The researchers say that their study provides convincing evidence that open access genetic testing overcomes major barriers; not just lack of family history, but also referral and bureaucratic barriers, and that it is acceptable to those likely to be affected and their families.

“We were concerned that ‘low risk’ participants, with no family history, might not be able to cope with being offered BRCA testing and particularly with positive test results. We also worried that being found not to be a carrier might provide false reassurance and cause women to think they had no cancer risk and therefore avoid standard surveillance. We were pleasantly surprised on both counts,” Ms Lieberman will say. In fact, mammography screening rates did not decline post-test in non-carriers, and even increased in some.

Falling prices for genetic sequencing and new techniques to avoid evaluating irrelevant gene variants will most likely make mutation screening available to wider populations in the near future. “We believe that our results are useful and highly relevant for other populations.  On a personal note, I hope that this new approach means that one day I will not have to counsel someone with no family history and therefore no awareness of increased risk who says to me that she only wished she had known before,” Ms Lieberman will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “This important study highlights the importance of population-wide genetic screening to identify women at risk of developing breast and ovarian cancer because of a genetic predisposition. The study also showed that most people cope very well with this genetic information; carriers of these mutations undertake breast cancer surveillance, whereas non-carriers are aware they can still develop breast cancer.’’


Abstract no:  C12.3

The research was funded by the Breast Cancer Research Foundation.

Balancing rights and responsibilities in insurers’ access to genetic test results

Copenhagen, Denmark:  Genetic testing is widely used across the developed world in order to diagnose and predict disease. However, along with its usefulness comes concern about how others, such as employers and insurers, can have access to and use its results. This in turn leads to the risk that individuals may avoid medically recommended genetic testing, or participation in genetic research, if they fear that they may be discriminated against based on their results.

At the annual conference of the European Society of Human Genetics tomorrow (Saturday), Anya Prince, JD MPP, a postdoctoral research associate at the Centre for Genomics and Society, University of North Carolina, Chapel Hill, USA, will present results of her study comparing the regulation of life insurers’ use of genetic information in the UK, Canada, and Australia.

“Such a study is necessary in order to appreciate the effectiveness and potential downsides of different policy options,” says Ms Prince, who hopes to use her results to inform the development of regulations addressing life insurer use of genetic information in the United States.  “Understanding which policy options most effectively assuage fear of discrimination has the potential to improve human health by encouraging individuals to undergo testing when medically recommended and to participate in genomics research.”

In Australia, private life insurers are permitted to use genetic test results when setting insurance rates and deciding whether or not to accept an application. Although they are only allowed to use test results based on actuarial or statistical data, they are free to use their own judgements as to which tests meet these requirements.

In Canada, while life insurers are currently allowed to use genetic test results, the Parliament recently passed legislation that would prohibit them from doing so when drawing up insurance contracts. But in Canada insurance regulation comes under the jurisdiction of the provinces, so there is some doubt as to whether this ban is constitutional. The legislation is currently under judicial review.

Of the three countries studied, the United Kingdom had the most comprehensive protection against insurer use of genetic information. Life insurers have agreed to a moratorium on the use of predictive genetic test results for life insurance policies below £500,000 (five hundred thousand pounds). Above this figure, insurers are allowed to use genetic tests sanctioned by a government advisory committee, but to date only Huntington’s Disease testing has been permitted.

“The two-tiered UK system is seen by many both within and outside of the country as being an effective way of balancing individual and insurer concerns—on the one hand about genetic discrimination and on the other about the economic viability of the industry. And the flexible nature of the moratorium, which is not permanent legislation, helps insurers feel comfortable that they will be able to react to advances in genomic research if necessary,” says Ms Prince.

However, discussions with insurers in Australia and Canada showed that they felt that to lose access to genetic test results would have a drastic effect on their industry, and could threaten financial collapse. Unsurprisingly, individuals in those countries were much more likely to fear discrimination as a result of genetic testing than those interviewed in the UK.

Ms Prince has now widened the scope of her study to include Sweden, where insurers are barred from taking genetic test results into consideration. “I hope this comparative research will help to foster international dialogue about the ethical and legal implications of genetic research and insurance. Personally, I think that a two-tier system, as implemented in the UK, creates an appropriate balance. If insurers are allowed to use test results, I believe their model of an independent committee controlling which test results they may use is necessary,” she says.

However, a major question remains. Are genetic test results relevant to insurance underwriting? “While genetic testing may promise to reduce risk, it is important to keep in mind that most genetic information can be affected by so many other factors. These include the environment, the likelihood of developing symptoms if someone has a genetic mutation (called the penetrance), the variation in signs and symptoms that can occur among people with the same condition, and how easy it is to minimise risks in individuals.”

“Where there are tests for highly penetrant conditions, it is relatively easy to predict outcomes, but these conditions affect only a very small percentage of the population. It is therefore unsurprising that there is active debate about how loss of access to genetic test results would really affect the economic viability of the insurance industry,” Ms Prince will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “Genetic testing is becoming more mainstream and providing an increasing amount of information that can be used to predict disease risks. It is therefore important to evaluate who may or may not have access to these data and for what purpose, and make sure we develop common rules that can be internationally applied and upheld. This work provides an important analysis of the way different countries deal with this. It points to considerable differences that need to be addressed with all stakeholders involved.”


Abstract no:  P20.03C

The research was funded by the National Human Genome Research Institute of the National Institutes of Health (USA) under Award No. K99HG008819.


Geneticists welcome Kuwaiti decision to amend law on compulsory DNA collection

For immediate release: Wednesday 19 October 2016

Responding to the decision of the Emir of Kuwait to request the Kuwaiti Prime Minister to reconsider the scope of the law that would have imposed compulsory DNA testing on all residents as well as visitors to the country, Professor Olaf Horst Rieß, President of the European Society of Human Genetics (ESHG), said:

“This is a wise and responsible decision. The law as originally proposed was disproportionate and likely to be ineffectual in tackling the problem of terrorism, and would have had negative consequences not just for Kuwaiti society, but also for medical science and research.”

Note to editors: Background to the law and the ESHG position can be found below.

ESHG Statement and Press release on the New Kuwaiti law on the collection of human DNA

New Kuwaiti law will severely affect international collaborations

Following  a terrorist attack, the Kuwait Government introduced a law mandating compulsory collection of DNA samples from its entire population (citizens, legal, and illegal residents), as well as foreign visitors. The law will also apply to tourists and visiting scientists, and will impose a one year

prison term and a fine on those who refuse to provide samples. This makes Kuwait the first country in the world to legislate for the mandatory collection of human DNA samples. Several important organisations have opposed this law and called upon the Kuwait government to amend it[i].

The President of the European Society of Human Genetics and the chair of the Professional and Public Policy Committee have sent a letter dated 31 August 2016 to His Highness Sheikh Jaber Mubarak Al-Hamad Al-Sabah and to The Council of Ministers of the State of Kuwait asking them to reconsider this law and to amend it so that human DNA is collected for legal purposes only from individuals suspected of having committed serious crimes. This would be in line with The European Convention on Human Rights, which in ARTICLE 8 on the Right to respect for private and family life states that:

1. Everyone has the right to respect for his private and family life, his home and his correspondence.

2. There shall be no interference by a public authority with the exercise of this right except such as is in accordance with the law and is necessary in a democratic society in the interests of national security, public safety or the economic wellbeing of the country, for the prevention of disorder or crime, for the protection of health or morals, or for the protection of the rights and freedoms of others. 

As the professional organisation bringing together human geneticists across Europe we are in agreement with the UN Human Rights Committee that such a law is disproportionate and violates the right to privacy. We understand that the current government is building the collection of human DNA samples for the protection of the Kuwaiti citizens. However, the simple existence of such a resource could be dangerous in the future, for example, if hacked or in the event of a régime change. 

Fears voiced in the media and elsewhere include the possibility of discrimination based on the attribution of ancestry, whether correct or wrongful. While many countries consider that a child’s rights are determined by the country of birth, fears are that DNA testing might lead to exclusion of persons not considered belonging to the country.

An additional concern is the potential effect of the compulsory testing of all visitors, including scientists. We believe that this is likely to lead to the isolation of Kuwaiti research institutions, as visiting scientists may refuse to give samples and therefore will not attend valuable scientific conferences in Kuwait, for example. We consider that the global challenges in human health and demography can best be addressed by all industrialised countries in a collaborative way. We see this new law as a major threat to joint actions in the field of genomic health that involve national European genetic societies.


[i] U.N. rights panel urges Kuwait to amend broad DNA testing law

GeneWatch UK PR: Expansions of police DNA databases worldwide urgently need human rights safeguards[cid]=566699&als[itemid]=576234

New Kuwaiti law on the collection of human DNA is contrary to human rights and threatens scientific collaboration, says ESHG

For immediate release: Thursday 8 September 2016

The law requiring compulsory DNA testing of all Kuwaiti residents, as well as of all those visiting the country for whatever purpose, is a serious assault on the right to privacy of individuals, and is also likely to lead to the isolation of Kuwaiti scientific research and researchers, the European Society of Human Genetics (ESHG) said today [Thursday 8 September]. In a letter addressed to the Prime Minister and the Council of Ministers of the State of Kuwait, the Society calls upon the government to amend the law.

According to the Kuwaiti government, the new measure has been introduced to try to tackle the problem of terrorism in the country.  It provides for the imposition of a one-year prison term and a fine on those who refuse to provide samples. “Not only does this law constitute a disproportionate response to the problem, but the very existence of such a comprehensive database of human DNA could be dangerous in the future, in the event of hacking or a regime change, for example,” said Professor Olaf Horst Rieß, ESHG President.

Another concern for the Society is the potential effect of the compulsory testing of all visitors, including scientists. “We believe that this is likely to lead to the isolation of Kuwaiti research institutions, as visiting scientists may refuse to give samples and therefore will not attend valuable scientific conferences in the country”, said Professor Rieß.  “The current global challenges in human health and demography must be addressed by all industrialised countries in a collaborative effort.”

“We see this new law as a major threat to joint actions in the field of genomic health that involve national European genetic societies, and therefore we request the Kuwait government to reconsider and to amend this law so that human DNA is collected for legal purposes only from individuals suspected of having committed serious crimes,” said Professor Martina Cornel, Chair of the ESHG Public and Professional Policy Committee.



Reproduction of an article in the New Scientist.

Kuwait’s mass DNA database is a huge attack on genetic privacy
The Gulf State will soon be the first nation to force all residents and visitors to hand over DNA, risking its reputation and more, warns geneticist Olaf Rieß

Could collecting DNA have prevented the suicide attack at this Kuwaiti mosque in June 2015? It’s hard to see how 

By Olaf Rieß

Compulsory DNA testing of all citizens and visitors sounds like an Orwellian nightmare, but this is the new reality in a wealthy Gulf State. Kuwait has become the first country to order blanket genetic sampling – a worry on so many fronts.

What happens if the DNA database is hacked? And even if the current government can keep the database secure, what might happen in the event of a regime change?

The Kuwaiti government says DNA testing, reportedly due to begin within weeks, is needed to combat terrorism, and introduced the measure in the wake of a bombing that killed 27 people there last year. While the need to have a swab taken may discourage attackers from entering the country, we should not forget that a lot of terrorism these days is home-grown. And who ever heard of a suicide bomber being dissuaded because they might be identified after blowing themselves up?

The government has also said the database could help identify victims. But if a bomb causes many fatalities, DNA will not help much in distinguishing the attacker from those killed. The terrorism argument is so spurious that even the least suspicious among us might begin to wonder whether there is an ulterior motive for this wholesale collection of DNA.

Let’s just try to imagine some of the other potential uses. Worrying examples spring easily to mind: checking paternity in a country with severe adultery laws or trying to uncover someone’s ethnic origin in order to discriminate. And we know from history that many initiatives that started out with the best of intentions have ended up used for nefarious purposes.

Matching names to genes: The end of genetic privacy?

It seems to me, too, that the Kuwaiti government could cause irreparable harm to the country’s economy and reputation. Tourists may not know that their DNA will be collected upon arrival; neither will they understand all that this implies. Some may accept the sampling, but others will choose to stay away.

There are implications for business and science. European industry and research has benefited hugely from the loosening of travel restrictions and the subsequent boosting of trade with Kuwait. Companies will now think twice about opening facilities there.

And will scientists from abroad still wish to attend conferences in Kuwait in the knowledge that their right to privacy will be invaded so dramatically? I think not. This could have a major impact on Kuwait’s standing as a conference host and hinder joint research projects.

As a scientist using genetics to seek medical advances, I also worry that compulsory collection of DNA might affect public willingness elsewhere to support research. If sampling becomes linked to coercion in the public eye, this is likely to reduce people’s readiness to include their genome in research databases, which are so important in the quest to better understand and treat disease.

Kuwait has invested heavily in genetic technology, so collecting DNA on this scale would probably be feasible, at least in the first instance. But the question is not whether it is feasible, but rather whether it is desirable.

The answer is clear; it is neither appropriate nor helpful in tackling the dangers it is designed to confront, and the threat posed in the event of its misuse is highly alarming.

Article amended on 12 September 2016
Since this article was first published, the context of some potential (mis)uses of DNA sampling in Kuwait has been made clearer.

Olaf Rieß is a medical geneticist and president of the European Society of Human Genetics, which has called on Kuwait to abandon blanket sampling

European Human Genetics Conference 2016, May 21-24, Barcelona, Spain

Loss of Y chromosome in blood cells is associated with developing Alzheimer’s disease: new research could lead to a simple test to identify those at risk

Embargo: 00.01 hrs CEST Tuesday 24 May 2016

Barcelona, Spain:  Men with blood cells that do not carry the Y chromosome are at greater risk of being diagnosed with Alzheimer’s disease (AD), and this is in addition to an increased risk of death from other causes, including many cancers, the annual conference of the European Society of Human Genetics will hear today (Tuesday). The paper is published today in the American Journal of Human Genetics*. The loss of the Y chromosome, or LOY, is known to affect up to 20% of men who are aged over 80, and is the most common genetic mutation acquired during a man’s lifetime.

Professors Lars Forsberg and Jan Dumanski, from the Department of Immunology, Genetics and Pathology at Uppsala University, Uppsala, Sweden, and colleagues from Sweden, France, the UK, the US and Canada, investigated LOY in over 3200 men with an average age of 73, and an age range of 37-96. Around 17% of them showed LOY in blood cells, and this increased with age. The researchers found that those with an existing diagnosis of AD had a higher degree of LOY, and that LOY was also a marker for the likelihood of developing the disease during the follow-up period.

“The idea for this research project came to me when I was writing our first paper on the relationship between LOY and the development of non-blood cancers,” Prof Forsberg explains. “In thinking about the process known as immunosurveillance – the body’s ability to fight disease development throughout life – I found that it had been well studied in AD, and hence it occurred to me that LOY might be involved in this disease too.”

Using standard molecular techniques, the identification of LOY in blood is easy to determine when it occurs in 10% or more of blood cells with a nucleus containing DNA. As well as being relatively common in older men, it also occurs less frequently in those who are younger.

Since women do not carry a Y chromosome, and men have, on average, shorter lives, it is possible that LOY may be related to the earlier death of men. However, the researchers say, the mechanisms and causes for their findings are still not properly understood.  They are currently investigating the functional effects of LOY, and looking at its role in different groups of men and in other diseases, in order to understand better which types of cancer are associated with LOY, as well as whether there is a link with early signs of dementia, for example mild cognitive impairment.

Another question to be answered relates to how LOY in blood cells can be related to disease in other organs. “The blood cells we studied are involved in the immune system, and the fact that LOY in them is associated with disease in other tissues is striking. We therefore hypothesise that the loss of LOY in blood cells leads them to lose part of their immune function,” says Prof Forsberg.

Previous research by the same group has shown that smoking greatly increases the risk of acquiring LOY, by as much as 400%. However, smoking appears to have a transient effect, and is also dose-dependent, so quitting could reverse the effect. This could be important to emphasise in smoking-cessation programmes, the researchers say.

More difficult to tackle is the question of diagnosis and treatment of serious conditions such as AD and cancer. This currently based on identifying clinical symptoms, and the development of diagnostic tools for their earlier detection could lead to strategies aimed at preventing their development before symptoms occur. For example, in the future it might be possible to use an LOY test to identify men at risk and then carry out oncological or neurological evaluations to try to detect early, mild, symptoms of disease. LOY might also become an important diagnostic tool in combination with other biomarkers that may be used to predict risks for various diseases.

“The addition of LOY testing in the general population could give medical practitioners the possibility of using preventive strategies in men at risk,” says Prof Forsberg. “For example, in cancer, primary tumours are usually not deadly; it is the metastatic process that it normally responsible for deaths. If we could predict which men have an increased risk of cancer, we could watch them closely for the development of disease and also use appropriate preventive treatments. In short, the widespread use of LOY testing could radically decrease male mortality rates, and even perhaps eliminate the difference in life expectancy between the sexes.”


Abstract no:  C23.1:  Mosaic loss of chromosome Y (LOY) in peripheral blood is associated with age, smoking, shorter survival and increased risk of cancer and Alzheimer’s disease


The research was funded by the European Research Council (ERC), Stiftelsen Olle Engkvist Byggmästare Foundation, Swedish Research Council (VR), the Wellcome Trust, Swedish Cancer Society, Swedish Heart-Lung Foundation, Science for Life Laboratory at Uppsala University, Uppsala University Hospital, Uppsala University, Heart and Lung foundation, GenomEUtwin, NIH, Swedish Foundation for Strategic Research (SSF), French National Fondation on Alzheimer’s disease and related disorders, Fondation pour la récherche sur le cerveau (FRC), Lille Métropole Communauté urbaine, LABEX and DISTALZ.

Discovery of new disease gene will lead to better screening for severe paediatric heart disease

Embargo: 00.01 hrs Tuesday 24 May 2016

Barcelona, Spain:  Cardiomyopathy, or a deterioration of the ability of the heart muscle to contract, generally leads to progressive heart failure. It is frequently inherited, and, because approximately 40% of children born with it are likely to die within five years of diagnosis, being able to identify its genetic basis is particularly important. Now, an international team of researchers has identified a new disease gene which is implicated in the development of severe paediatric cardiomyopathies. The gene is probably also involved in a milder, adult-onset form of the condition.

Presenting the results of the study to the annual conference of the European Society of Human Genetics today (Tuesday) Johanna Herkert, MD, a clinical geneticist at the University Medical Centre of Groningen, The Netherlands, will describe how analysis of the exomes (the parts of the genome that produce proteins) of children who were seriously ill with early-onset cardiomyopathies led to the finding that a mutation in the gene alpha-kinase 3 (ALPK3) had been inherited from both their fathers and mothers. In cases where both parents carry the mutation, the risk of having a child with a severe cardiomyopathy is 25%. Since the child does not carry a normal copy of gene the condition will develop at an early age.

“However, several family members who carried only one mutated gene copy also developed cardiac disease, albeit at a later stage in life,” says Dr Herkert. “The identification of these mutations enables us to provide genetic counselling, predictive testing of family members, and prenatal testing in future pregnancies. It also allows us to provide early treatment, and a potential target for drug development in the future.”

The researchers studied five children with cardiomyopathy from three unrelated families of different ethnic backgrounds. The families had previously been screened for mutations in other cardiomyopathy-related genes. Four patients were diagnosed during foetal life, or within hours of birth, and the fifth only developed symptoms at four years old. Three of the children died between 35 weeks of gestation and five days of birth; the other two were still alive at 11 years old, but showed signs of severe cardiomyopathy.

“We knew that mice without a functional ALPK3 gene displayed very similar cardiomyopathy related features to those observed in our paediatric patients,” says Dr Herkert, “but we did not quite know how dramatic its effect would be in humans. Our findings show that we now should include this gene in routine diagnostic screening in order to be able to identify affected children and their family members at risk. This will also give us an insight into the prevalence of ALPK3-related cardiomyopathy in the general population.”

Although the possibility of treating an affected foetus in the womb is still a long way off, the gene could provide a drug development target for a medicine to be administered immediately after birth before the disease has a chance to develop further. Affected family members with only one ALPK3 mutation could also be treated later in life.

“We are currently studying the effect of the ALPK3 mutations on the production of the protein in heart muscle, but also in skeletal muscle, as ALPK3 gene mutations may result in skeletal muscle problems too. Moreover, a large genome study has shown a possible link between ALPK3 and cardiac hypertrophy, or thickening of the heart muscle. We would like to explore this finding further as it may well mean that ALPK3 is implicated in other heart diseases in the general population, and once again this could suggest new treatment possibilities.

“Better knowledge of the precise role of the gene in disease development, as well as the elucidation of the molecular pathways involved, should lead us towards improved clinical care from the point of view of screening and surveillance, and to targeted drug development,” Dr Herkert will conclude.


Abstract no:  C22.2

Dietary experiments in mice point the way to early detection of cancer development in humans

Embargo: 00.01 hrs CEST Monday 23 May 2016

Barcelona, Spain:  Colorectal cancer is the second most common cause of cancer-related deaths in the Western world, mainly because it is usually diagnosed too late. Finding ways to identify those people who are at increased risk of developing colon cancer is therefore crucial, a researcher will tell  the annual conference of the European Society of Human Genetics today (Monday).

Marjaana Pussila, a PhD student in the ‘DNA mismatch repair and cancer’ group at the University of Helsinki, Finland, will explain how her team’s work in genetically-engineered mice has helped to reveal the role played by a Western-style diet, rich in fat and low in fibre, vitamin D and folate, in the development of colorectal cancer.  Interactions between genetic and environmental factors, including diet, are thought to play a crucial role in its development, but the earliest changes in normal colonic mucosa that could lead to early detection and prevention of cancer development remain to be elucidated.

Using a mouse model of Lynch syndrome, the most common form of inherited colon cancer, the researchers carried out a long-term diet experiment. The Lynch syndrome mouse carries a mutation in MIh1, a mismatch repair gene, which is one of the main susceptibility genes in the disease. Each time cells divide, DNA has to replicate itself. It is during this process that mistakes can be made, leading to genomic instability and potentially to cancer. Lynch syndrome carriers have inherited one healthy and one mutated mismatch repair gene, and about an 80% risk of developing cancer.

“We wanted to be able to spot cancer-predicting events in the colon mucosa before tumours developed,” Ms Pussila explains. “For this reason, we decided to use a mouse model which was already known to have a susceptibility to colon cancer. We reasoned that in mutation carriers requiring just a second hit of the inherited susceptibility gene for malignant transformation, it might be possible to detect the earliest changes, perhaps even preceding the second hit, and distinguish these from alterations occurring later in cancer development.

“Interestingly, our results showed that the gene expression profiles of normal mucosa in those mice that developed colon cancer were very different from those of the mice that did not. This seems to indicate that there is a colon-wide effect of events that predispose to cancer.  And the Western-style diet seemed to be a severe risk factor, since 80% of cancers were detected in WD fed mice,” says Ms Pussila.

Surprisingly, no typical Lynch syndrome tumour characteristics, such as lack of MIh1 protein or microsatellite instability – a kind of genetic hyper-mutability – were detected, although MIh1 gene expression was already severely decreased in the mucosa. This suggests that a decrease in MIh1 gene expression may be sufficient to induce the development of tumours, even where the DNA mismatch repair mechanism that recognises and corrects mistakes in DNA replication is still operating well enough to avoid microsatellite instability.

“It has been generally assumed that the development of cancer in Lynch syndrome carriers needs an inactivation of both the mismatch repair gene alleles, or pairs, involved, thus causing microsatellite instability. However, our studies have shown that this is not necessarily the case, since a severely decreased amount of MIh1 without loss of the second allele and without microsatellite instability appears to be enough to provoke the development of tumours,” says Ms Pussila.

“Now, by studying the gene expression profiles of Mlh1 low mucosa we hope to be able to  further identify cancer predisposing changes which may help in early detection of tumours,” Ms Pussila will conclude.


Abstract no:  C14.1 – Lynch syndrome mouse: A model for colon carcinogenesis


The research was funded by grants from the European Research Council (2008-AdG-232635) and the Jenny and Antti Wihuri Foundation.

How does obesity cause disease in organs distant from those where fat accumulates? New genetic evidence points the way

Embargo: 00.01 hrs CEST Sunday 22 May 2016

Barcelona, Spain:  Obesity is on the rise throughout the world, and in some developed countries two-third of the adult population is either overweight or obese. This brings with it an increased risk of serious conditions such as heart disease, stroke, cancer and osteoarthritis. Many of these conditions do not appear to affect the parts of the body where the excess fat accumulates, but rather to involve body systems that are remote from the fat accumulation. Now an international group of scientists has taken an important step towards understanding the links between obesity and the related, yet physically distant, diseases it causes, the annual conference of the European Society of Human Genetics will hear today (Sunday).

Ms Taru Tukiainen, D.Sc., a postdoctoral researcher working at the Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland and colleagues from the UK and US, set out to study the relationship between body mass index (BMI), a common-used way of measuring obesity, and gene expression in 44 different tissue types, including some that are rarely accessible in large sample sizes, for example the brain and internal organs. “Most tissue sampling is invasive, but we were able to use the GTEx* dataset of tissues from autopsy donors, and therefore sample a far wider range than is usually possible,” Ms Tukiainen explains. “This is the first time that such changes in human tissue function in response to alterations in BMI have been explored among so many body systems simultaneously.”

The researchers found simultaneous changes in response to obesity in almost all the tissues studied. “These results show that obesity really is a systemic condition, and particularly a condition of systemic inflammation. Interestingly, though, the changes in tissue function appeared to be only partially shared between different types of tissues; some tissues clearly act in pairs with one half of the pair compensating for – or enhancing - the dysfunction of the other. For instance, adipose tissue and adrenal glands, which are both organs secreting hormones essential to metabolism, often react to changes in BMI in completely opposite ways, including a decrease in metabolic activity in the former and an increase in the latter,” Ms Tukiainen will say.

Although lifestyle changes are the most effective way to combat obesity, they can be hard work and difficult to maintain. Therefore the biological processes identified by the researchers may help the treatment of obesity by identifying potential drug targets, and particularly tissue-specific targets, they say. The results may also help to distinguish groups of individual who are at higher risk of developing complications, and lead toward personalised care.

“Our research highlights the burden of overweight and obesity on the digestive system. Although this is unsurprising, given the role of digestive system tissues in food processing, we found alarming links between BMI-related changes in different parts of the digestive tract and genes implicated in some diseases, for example Crohn’s disease.

“An association between two variables does not necessarily imply there is a causal link and, from the gene expression results alone, we cannot tell which is driving which. Do changes in BMI or changes in gene expression come first? We can, however, address the potential causes by using genetic variants known to be associated with BMI in combination with our data on gene expression,” says Ms Tukiainen.

Large-scale genome-wide association studies have already identified nearly 100 genetic variants that influence BMI. Analyses by the group that interpret this information further have shown that many of these gene expression changes, particularly in adipose tissue, appear to be caused by increased BMI.

“I believe that our work adds to the weight of evidence, and provides hypotheses for other researchers to follow up in the hope of being able to translate the results into ways of preventing and treating the very serious complications of obesity,” Ms Tukiainen will conclude.


*GTEx is a dataset consisting of thousands of tissue samples in which the RNA from each sample has been sequenced to measure gene expression. Because it is not a dataset collected specifically for obesity research, the donors are representative of the population as a whole, and the obesity epidemic is clearly reflected in that only 31% of GTEx donors are or normal weight; the remainder are either overweight or obese.


Abstract no:  C08.1 – Multi-tissue transcriptome analysis reveals disease-relevant and causal links between obesity and gene expression


GTEx is funded by the US National Institutes of Health. Ms Tukiainen is funded by the Academy of Finland.

Mouse studies hold promise for a simple, non-surgical treatment for an aggressive gastric neuroendocrine tumour

Embargo: 00.01 hrs Friday 20 May 2016

Barcelona, Spain:  Patients with aggressive neuroendocrine tumours (NETs) have limited treatment options and there are few oncologists who are specialised in this relatively rare disease. Normally a total gastrectomy (removal of the stomach) is employed in these cases, with a subsequent dramatic reduction in the quality of life for patients. Now researchers have identified a mutation in the human ATP4a gene that is involved in the gastric acid secretion regulation and has been identified as responsible of an aggressive form of inherited, early-onset gastric NET.  

Dr Oriol Calvete, from the Human Genetics Group at the Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain, will present his work to the annual conference of the European Society of Human Genetics tomorrow (Saturday). “Our research has enabled us to determine important clinical ‘red lights’ for the early diagnosis of patients who will develop these tumours at a younger age, and to identify characteristics that distinguish a good from a poor prognosis for these patients,” he says.

The researchers generated a genetically-engineered mouse carrying the mutation. This developed most of the changes seen in human patients, including not just achlorhydria (a lack of or total absence of gastric secretions in the stomach), but also iron-deficiency anaemia and other pathological changes that replicate the human clinical traits involved, through the presence of which the researchers were able to confirm the mutation as the primary one responsible for the development of gastric NETs.

The researchers were able to restore chlorhydria in affected mice by adding a 3% solution of hydrogen chloride to their drinking water.  Mice that drank this water from birth did not develop gastric NETS, and in those where treatment was started later in the life cycle, the main causative biochemical alterations responsible for their development were blocked. “Gastric acid regulation is quite complicated,” Dr Calvete explains.  “Because gastric secretions are activated by the intake of food via the stomach, there are no signs of being abnormal before birth, but by restoring normal gastric acid balance as soon as possible afterwards, we can eliminate the conditions that lead to the development of tumours.”

NETS develop in the neuroendocrine system that is responsible for producing the hormones that regulate the working of different organs in the body. They are rare, incurable, and treatments for them are limited, especially once they become advanced. Because all NETS are classified as rare diseases by regulatory authorities in the EU and the US, there are few drugs available to treat these patients.

“The younger age of onset – around 30 years - of this particularly aggressive form of gastric NET in humans means that it is particularly important to try to find a treatment that is relatively simple, cheap, and does not compromise quality of life,” says Dr Calvete. “Total gastrectomy at 30 years old can have a devastating effect, and because NETS are highly infiltrating tumours, does not always mean that it will avoid metastasis. We hope that our work has given a lead towards a way of avoiding patients having to undergo this kind of aggressive surgery.”

“Additionally, the genetically-engineered mouse model will allow us to test potential treatments aimed at correcting achlorhydria, not just for gastric NETS, but also for other diseases of the gastrointestinal system such as Barrett’s oesophagus (chronic inflammation of the lower part of the oesophagus), or hiatus hernia,” says Dr Calvete.

The researchers are now intending to carry out further investigations into the genetic causes of other gastric NETS.  “For example, we have studied two more families with similar pathological characteristics, but with no mutation in the ATP4a gene. This implies that other genes may be  responsible and we hope to discover them using a similar methodology,” Dr Calvete will conclude.


Abstract no:  P12.098B


The research was funded by the Spanish Center for Biomedical Network Research on Rare Diseases (CIBERER), by the European Commission’s Horizon 2020 (BRIDGES project) and by the Spanish Government’s Proyectos de investigación en Salud (PIS) PI012-00070.


EU Regulation on Medical Devices still poses dangers to patients’ interests, says ESHG

For immediate release

The proposed Regulation on In Vitro Diagnostic Medical Devices (IVDs) negotiations, currently at the stage of tripartite negotiations between the Council (representing Member State governments), the European Parliament, and the European Commission, still risks restricting the rights of patients and doctors to carry out essential genetic testing, says the European Society of Human Genetics (ESHG) today (19 October 2015) in a statement issued by a range of organisations representing geneticists and patients.

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ESHG 2015 Conference Press Release: People want access to their own genomic data, even when uninterpretable

Glasgow, United Kingdom:  The largest study to date of attitudes towards the use of genomic information shows that the majority of people want access to results from genome sequencing, even if these are not directly related to the condition for which the analysis has been undertaken.  This applies even when the data are not health-related or are simply ‘raw’, a researcher will tell the annual conference of the European Society of Human Genetics today (Monday).

Dr Anna Middleton, a Principal Staff Scientist at the Wellcome Trust Sanger Institute, Cambridge, UK, will describe the results of a survey into the attitudes of the various groups involved in sequencing research – patients, public, health professionals, and genomic researchers – towards the types of genomic information they would be interested in receiving.  Just under 7000 people from 75 countries took part in an on-line survey, advertised on social and traditional media, and by an email list-serve.

“We asked participants to imagine that they were taking part in sequencing research with the option to receive personal results, and carefully explained the sorts of results that might come from a sequencing study in ten short films. We found that 98% of participants wanted to know about genes linked to treatable conditions that were serious or life-threatening; they were still interested even if the chance of such a condition occurring was as low as 1%. What was important to them was being ‘forewarned’ about their future risk of disease so that they could take steps to protect their health. This makes sense, but we also found that 59% of those surveyed were interested in having access to their own raw data, even though, on its own, it would tell them nothing useful about their future health. Participants perceived a value a value in raw data that may or may not exist:  ‘if the scientists know it, I’d like to know it too.’ They felt the genomic information simply ‘belonged to them’ and thus they should be able to have access to it, even if the reality was that they would do nothing with it,” Dr Middleton will say.

Participants appeared to be excited and positive about genomics, and they also wanted to be connected to the research process; for example, they were keen that genomic researchers should keep re-analysing their data and report to them if there were new findings. But they also recognised that scientists had an important job to do in doing good quality research; the work of answering a particular research question should not be side-tracked by a necessity to supply personalised results. Participants said they were willing to forego the return of individual findings if the delivery of such data compromised the ability of scientists to focus on the answer to a research question.

“It would now be very helpful to explore the value that people put on genomic data. For example, would they pay for an interpretation and, if so, how much?” says Dr Middleton. “Creating clinical-grade health information in a research setting requires funding, resources, and strong clinical connections to the health professionals who will deliver it, explain it, and follow up the patient. This may be out of reach for many researchers. So if research participants expect personalised results, but they also don’t want researchers to compromise their research in order to deliver such results, then would they be willing to pay for these services?

“What we did in our research is explore what people say they might do in a hypothetical situation, and what we need to do next is explore the actual experience of research participants who are given personal results from sequencing research. We know already that some research participants ask for their raw sequence files and so it would be really useful to follow such participants over time to see what they do with these. We also want to know more about the psychosocial impact of receiving genomic data and whether it has an emotional resonance that people didn’t expect.

 “Researchers have a responsibility not to harm their research participants, and if they are going to provide results, they need to do this in an ethical way. At the moment our genomics community agrees that if researchers choose to return results that could potentially be clinically actionable these need to be confirmed in a clinically accredited laboratory before they are returned, and there should be a clinician available to share the information with the patient and to provide screening services if necessary. For research participants who ask for their raw sequence data (that by their very nature, come with no interpretation), then they should be given a clear explanation of the limits of these data together with some signposts to services that they can access for interpretation and support. Without this there is a risk that research participants will turn up at the door of their GP and ask them what it all means.” Dr Middleton will say.

“Whilst I feel that autonomy is important, and research participants do have the right to their own data, should they want them, we also have a responsibility to explain the reality of the difficulties with interpretation – and to do this without misleading people. By allowing research participants access to raw sequence data, they have the choice as to how these are explored and what sorts of information they would like to glean from them. However, they can only really do this when there is easy access to interpretation services that can be endorsed by health professionals and genomic researchers alike. Such services are not easily accessible currently and there is an urgent need to address this if sharing raw sequence data becomes a reality. Some of our participants mistakenly thought they could put their data into Google and an interpretation would pop out. Researchers mustn’t leave their participants stranded, so they should only share raw sequence data together with an explanation of what can be done with this. We also have to think carefully about the potential impact of this on health services,” she will conclude.


Abstract no:  C14.5 

Anna Middleton is a member of the Deciphering Developmental Disorders (DDD) project ( The DDD project is funded by the Health Challenge Fund, a partnership between the Wellcome Trust and the UK Department of Health.

ESHG 2015 Conference Press Release: Non-invasive prenatal testing: effective, safe, preferred by parents, and applicable in a range of disorders

Glasgow, United Kingdom:  Non-invasive prenatal testing (NIPT) for Down’s syndrome is feasible, acceptable to parents, and could be introduced into the National Health Service (NHS), UK researchers say. The results of a National Institute for Health Research (NIHR) study carried out by the first NHS laboratory to provide NIPT testing will be reported to the annual conference of the European Society of Human Genetics today (Saturday).

Presenting her team’s findings, Professor Lyn Chitty, from the UCL Institute of Child Health and Great Ormond Street Hospital, London, UK, will announce the results of the study evaluating the possibility of introducing NIPT into the NHS screening programme for Trisomy 21 (Down’s syndrome). The researchers will present their study to the UK National Screening Committee later this month and hope that it will inform their decisions on if and how to implement NIPT in the NHS.

As part of the study, carried out by the NHS laboratory at Great Ormond Street Hospital, women at high and medium risk of having a child with Down’s syndrome were offered NIPT, and over 2,500 undertook the test.

Prof Chitty says: “There was a very high uptake of testing and we saw invasive test numbers fall sharply. NIPT performed well in identifying problems, and women were very positive about it.

“The cost of providing an NIPT service will depend on the cost of the test itself and how it is implemented. There will be significant savings resulting from a decrease in invasive testing whilst increasing the detection of affected babies. The reduction in invasive testing also means there will be a reduction in miscarriages and loss of unaffected babies which is much better for parents.”

Commenting on NIPT, a woman classified as ‘high risk’ who was involved in the study said: “You get told 1 in 30 and although that sounds relatively high…we probably wouldn’t have done [invasive testing] because there’s a risk of miscarriage. ..I think that we were very lucky. It’s enabled us to make an informed choice about what happens for the rest of our lives.”

Another woman involved in the study said: “I think it’s a real advancement. At the moment, if you are put in a high risk category you’re automatically offered the invasive test, whereas this will reduce the amount of invasive tests that need to take place.”

Reporting the results of a second study from the same group, Dr Suzanne Drury, a translational research and development scientist from Great Ormond Street Hospital, will describe the team’s experience in the use of NIPD (non-invasive prenatal diagnosis) to diagnose the disorder congenital adrenal hyperplasia (CAH). CAH exposes a female fetus to male hormones, which can result in the development of masculinised external genitalia. It is an autosomal recessive (AR) disorder, in which the defective gene must be passed on from both parents in order to cause disease.

Dr Drury will say: “We chose CAH because the gene that causes it is particularly challenging to study. It is the most common adrenal disorder in childhood and affects one in every 18,000 live births. In the UK, NIPD for fetal sex determination is carried out for an average of 13 pregnancies per year at risk of CAH because it is the female fetuses that are at risk.

“Fetal sex determination allows targeting of invasive testing to see if the female fetus is carrying two mutant copies of the CAH gene and is therefore affected. As we were already carrying out NIPD for sex determination, and there is a potential in utero treatment for CAH available, we felt that this was a good condition to select to allow treatment to be very specifically targeted to only those female fetuses that are affected.”

In 2014, the researchers say, 32% of prenatal diagnostic tests for monogenic disorders in their laboratory were non-invasive.  NIPD for single gene disorders in a fetus is diagnostic, as it targets specific genetic changes present in a high risk family. For this reason it will remove the need for invasive testing completely, reducing the risk of miscarriage and making prenatal diagnosis for these conditions safer and more accessible to families who would not otherwise be prepared to take the risk.

Dr Drury adds: “Our results have shown NIPD to be sufficiently precise to be diagnostic and therefore we do not recommend confirmatory invasive testing. Currently we are developing non-invasive tests for other conditions caused by mutations in a single gene, including cystic fibrosis, sickle cell anaemia, and beta-thalassaemia.  At present invasive testing is required for definitive prenatal diagnosis of these disorders, but our experience with CAH leads us to believe that NIPD will have the same diagnostic efficacy in other AR disorders.”


Abstract nos:  C01.1 and C01.3


Prof Chitty’s work was funded by National Institute for Health Research (NIHR) Programme Grants for Applied Research (RP-PG-0707-10107), the NIHR Biomedical Research Centre at Great Ormond Street NHS Foundation Trust, and the Great Ormond Street Hospital Children’s Charity.

Dr Drury’s work was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research (RP-PG-0707-10107), the NIHR Biomedical Research Centre at Great Ormond Street NHS Foundation Trust, and the Great Ormond Street Hospital Children’s Charity.

ESHG 2015 Conference Press Release: Non-invasive prenatal foetal testing can detect early stage cancer in mothers

Glasgow, United Kingdom:  Non-invasive prenatal testing (NIPT) for chromosomal foetal disorders is used increasingly to test for conditions such as Down’s syndrome. NIPT examines DNA from the foetus in the mother’s blood, and therefore does not carry the risk of miscarriage involved in invasive testing methods. Now, for the first time, researchers have found another advantage of NIPT; it can detect maternal cancers at an early stage, before symptoms appear. The study, to be presented to the annual conference of the European Society of Human Genetics today (Saturday), is published simultaneously in the journal JAMA Oncology.

Nathalie Brison, PhD, a senior scientist in the Clinical Cytogenetics laboratory at the Centre for Human Genetics, UZ Leuven, Leuven, Belgium, will tell the conference that the team had set out to increase the accuracy of the NIPT test in order to overcome some of the technical problems that can cause it to come up with false negative or false positive results when screening for chromosomal disorders in the foetus. Down’s, or trisomy 21, is the most frequent chromosomal abnormality, and occurs in about one in 700 live-born babies. The risk of giving birth to a baby with Down’s increases with the age of the mother, and rises sharply from the age of 36 years.

“We therefore felt it important that we improved the accuracy of the test,” Dr Brison says.  ”Even though it is very reliable, we believed that we could make it even better, and in doing so we could also find other chromosomal abnormalities apart from the traditional trisomy syndromes - Down’s, Edward’s (trisomy 18), and Patau (trisomy 13). Using the new, adapted test in over 6000 pregnancies, and looking at other chromosomes, we identified  three different genomic abnormalities in three women that could not be linked to either the maternal or foetal genomic profile. We realised that the abnormalities bore a resemblance to those found in cancer, and referred the women to the oncology unit.”

Further examination, including whole body MRI scanning and pathological and genetic investigations, revealed the presence of three different early stage cancers in the women:  an ovarian carcinoma, a follicular lymphoma, and Hodgkin’s lymphoma. Although this incidence is within the range to be expected in the normal population (one per 1000-2000 person years in women aged 20 – 40), without NIPT these cancers would have been unlikely to have been detected until they became symptomatic, and therefore at a much later stage.

“Considering the bad prognosis of some cancers when detected later, and given that we know that it is both possible and safe to treat the disease during pregnancy, this is an important added advantage of NIPT,” comments principal investigator Professor Joris Vermeesch, Head of the Laboratory for Cytogenetics and Genome Research at Leuven. “During pregnancy, cancer-related symptoms may well be masked; fatigue, nausea, abdominal pain, and vaginal blood loss are easily interpretable as a normal part of being pregnant. NIPT offers an opportunity for the accurate screening of high risk women for cancer, allowing us to overcome the challenge of early diagnosis in pregnant women.”

Two out of the three diagnosed women were treated, one of them during her pregnancy. She subsequently gave birth to a healthy girl. The third had indolent disease that was not considered to be in need of treatment at that stage. Follow-up investigations in the treated women showed that NIPT had the additional advantage of allowing the effectiveness of treatment to be monitored, and the researchers were able to see that the chromosomal profiles became normal during and after chemotherapy.

Because the procedure involves looking at chromosomes other than 13, 18, and 21, women taking part were informed about the possibility of incidental findings. “However, our study feeds into the ethical debate about whether or not to report incidental findings to patients, and also has implications for the current political discussions concerning reimbursement and funding of NIPT by national health care systems,” says Prof Vermeesch.

The results suggest that NIPT might enable the detection of pre-symptomatic cancers not just in pregnant women, but more widely. “We now know that it is possible to offer the accurate detection of chromosomally imbalanced cancers to the general population via minimally invasive screening methods,” says Dr Brison. “The normalisation of the NIPT profile in these patients following treatment indicates that we can also measure response to treatment as early as after the first administration of chemotherapy.  Of course, larger scale studies will be required to validate these results further, but we are confident that we have made an important step towards the possibility of wide-scale, effective, non-invasive cancer screening capable of detecting disease at an early stage.”


Abstract no:  C01.5

The work was funded by the University of Leuven, the Belgian Cancer Plan (Ministry of Health), and the Belgian Science Policy Office.

ESHG 2015 Conference Press Release: First national study of non-invasive prenatal testing shows it works and is preferred by high-risk women

Glasgow, United Kingdom:  Results from a national study of non-invasive prenatal testing (NIPT) in women at high risk of having a baby with Down’s syndrome will be presented at the annual conference of the European Society of Human Genetics today (Saturday). The Netherlands is the first country in the world to include NIPT in a government supported, healthcare-funded trisomy syndrome screening programme. In many other countries, such screening is offered by commercial companies and without governmental guidance, so studying the accuracy of the programme and its acceptability to prospective parents was important, the conference will hear.

Dr Erik Sistermans, head of the Genome Diagnostics department, VU Medical Centre Amsterdam, The Netherlands, will present results from the TRIDENT (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing) study, of which he is the project leader.  Together with colleagues from other academic centres in The Netherlands, he formed a consortium including all stakeholders – gynaecologists, clinical geneticists, midwives, and laboratory specialists – to apply for the ministerial licence which is needed to screen for untreatable disorders such as Down’s.

 “The study was in two parts; first concerned with its implementation in eight university laboratories, and the second to examine the perspective of pregnant women. After receiving positive advice from the Health Council, a temporary licence for two years was granted allowing us to enrol women with an elevated risk of carrying a foetus with three syndromes caused by the presence of an abnormal number of chromosomes - Down’s (trisomy 21), Edward’s (trisomy 18), and Patau (trisomy 13),” Dr Sistermans will say.  Entry to the study was based on the results of a combined test, taking account of maternal age and involving a blood test and a nuchal fold measurement – a measurement of a skin fold in the neck of the foetus.

After nine months, 3306 high-risk pregnant women had undergone NIPT and 3278 reports on the status of the foetus issued. The researchers found 89 cases of trisomy 21, 11 of trisomy 18, and ten of trisomy 13. Follow up of 103 cases revealed only nine false positives.

Although NIPT carried a much lower risk of miscarriage than do invasive tests, it is slightly less accurate, because it only analyses DNA from the outer layers of the placenta. In some cases a trisomy will be present in these outer layers, but not in the foetus. “For this reason a positive NPT result should always be followed by an invasive test,” says Dr Sistermans. 

 “Currently the costs for NIPT and invasive tests are about the same, but we believe that with a greater uptake of NIPT the cost will fall. Given that the vast majority of the women we surveyed preferred to undergo NIPT in order to be more certain of avoiding risks to the child, it seems likely that the demand for this test will increase over the years to come.”

The researchers now expect the Dutch Heath Ministry to continue the offer of NIPT as a second test to women at high risk of carrying a child with a trisomic disorder. “Whether NIPT will be offered as a first screening test to all pregnant women is currently under debate, and will depend partly on the reaction of the health ministry to our study. Based on our findings, the TRIDENT consortium believes this test can benefit all pregnant women, not just those who are identified as being at risk, and has applied for a licence to offer it to them,” Dr Sistermans will conclude.


Abstracts no:  C01 and PS01.49

The research was funded by the Ministry of Health, the Dutch health insurance companies, and the Netherlands Organisation for Health Research and Development (ZonMw).

ESHG 2015 Conference Press Release: Discovery of new genetic mutation in aortic disease allows better diagnosis and brings personalised medicine a step closer

Glasgow, United Kingdom:  Thoracic aortic aneurysm and dissection (TAAD), an enlargement or tearing of the walls of the aorta in the chest, is, together with abdominal aortic aneurysms, responsible for about 2% of all deaths in Western countries. The aorta is the largest artery in the body, and carries blood from the heart. About one out of every five patients with TAAD has a family member with the same disorder, therefore indicating a genetic cause.  However, the relevant genetic mutations discovered so far only explain about 30% of all cases.  Through the study of a large family with TAAD features, an international team of genetic researchers have now discovered that a mutation in the TGFB3 gene is also responsible for the condition.

Elisabeth Gillis, MSc, a PhD student in the Centre for Medical Genetics at Antwerp University Hospital, Antwerp, Belgium, will tell the annual conference of the European Society of Human Genetics today (Saturday) that she and colleagues from seven other countries are the first to link this particular genetic mutation to serious aortic disorders.  This is important, she says, because it means that the TGFB3 gene can be included in diagnostic screening.  “Armed with this knowledge, we can screen patients with symptoms of TAAD, and also family members without symptoms. Early identification of a risk of aortic aneurysm formation will allow us to implement preventive treatment with medication aimed at slowing down the process of aneurysm and, ultimately, replacement of the aorta before a significant risk of dissection arises”, she will say.

An aortic aneurysm occurs where there is a weakness in the walls of the aorta, creating an outward bulge. Weakness in the aorta is dangerous, because it can lead to rupture (dissection) which is life-threatening.

The researchers studied 9 patients from a large Flemish-Dutch family with the cardiovascular, skeletal and facial features typical of a form of TAAD, called Loeys-Dietz syndrome.  They screened DNA from each family member without finding any genetic mutations known at that stage to be connected with TAAD.  However, further investigation revealed two candidate genomic regions that appeared to be involved, one of which contained the TGBF3 gene. “This gene was an obvious candidate because it has previously been shown that the TGFbeta-signalling pathway has a key role in the formation of aortic aneurysm,” says Ms Gillis.

After sequencing the gene, the researchers identified a mutation that was present in all affected family members. Finally, 470 TAAD patients were screened for TGFB3 mutations, and causal mutations were found in ten other families.

“This is an important finding because incidence of TAADs may be much higher than currently reported,” says Ms Gillis. “Acute aortic dissections may be disguised as heart attacks, and we know that the genetic component of TAAD is strong – in about 20% of patients, it is also found in family members. Therefore anything we can do to enable early identification of people at risk will help. However, aortic aneurysm formation is not yet fully understood, so reversing the risk of dissections remains a challenge, even though effective treatments are available.”

The choice of treatments for TAAD depends on a number of factors, such as size/location of the aneurysm and rate of growth. Current therapies include surgery, for example replacing the weakened part of the aorta, and medical treatments such as beta-blockers or angiotensin receptor blockers.

“Research on the TGFbeta-pathway in TAAD is far from finished. In addition to investigating further the role of these mutations in the condition, the discovery of new TGBF3 patients will help us improve follow-up guidelines for them. We hope that the identification of these new genetic factors will speed progress towards truly personalised medicine. The more we can link mutated genes to specific patients, the more we can identify the right symptoms and link specific therapies to them,” Ms Gillis will conclude.


Abstract no:  C05.2 

The research was funded by the European Research Council, the Fondation Leducq, the University of Antwerp, and the Fund for Scientific Research, Flanders.

ESHG 2015 Conference Press Release: Novel genetic mutations may arise during early embryonic development rather than being acquired from the parents’ germline

Glasgow, United Kingdom: New, sophisticated gene sequencing techniques are leading to an increasing understanding of the causes of genetic disease, and can help parents with affected children make informed reproductive choices, the annual conference of the European Society of Human Genetics will hear today (Saturday).  Until now, de novo genetic mutations, alterations in a gene found for the first time in one family member, were believed to be mainly the result of new mutations in the sperm or eggs (germline) of one of the parents and passed on to their child.

Using whole genome sequencing technology, researchers from The Netherlands have now succeeded in determining that at least 6.5% of de novo mutations occur during the development of the child (post-zygotic) rather than from the germline of a parent.  The research is published today in the American Journal of Human Genetics.

Christian Gilissen, PhD, Assistant Professor in Bioinformatics at Radboud University Medical Centre, Nijmegen, The Netherlands, will tell the conference that, due to the technical difficulties of identifying and validating post-zygotic events, until now there have been very few estimates as to how common they are. “Determining exactly how many mutations occur during the development of the child has been challenging because conventional genetic sequencing is not sensitive enough to reliably identify post-zygotic mutations,” he will say. 

Unlike germline mutations, the post-zygotic genetic changes are only present in a proportion of the cells of the individual. This is important because the proportion in  which the de novo mutation is present in a patient, as well as the type of cells in which it occurs, may not only determine the clinical outcome of a disease for the patient, but also affect the risk of the parents  having another child with the same disease in future pregnancies.

 “Currently, patients with a child with a disease caused by a de novo mutation are counselled that the risk of recurrence due to the same mutation in another child is between 1 and 5 percent, but if the disease is the result of a post-zygotic change, the recurrence risk will be extremely low,” says Dr Gilissen.  Better information on the origin of de novo mutations will enable better information on recurrence risk, and will enable parents to make more informed reproductive choices.

It is difficult at this stage to foresee the full impact of post-zygotic mutations in terms of treatment options for disease because the study was mainly focused on the technological aspects of these genetic changes, the researchers say. “The knowledge that our genomes may be much more dynamic and changeable than previously thought and the ability to detect such changes by using sophisticated sequencing techniques will certainly have clinical implications in the future.  It may also be reasonable to assume that post-zygotic mutations restricted to specific types of cells, or organs, may also be involved in causing disease.

“We now also know that for us to be able to find post-zygotic mutations, our sequencing needs to be even more sensitive. We intend to follow up this work by trying to get yet more detail on the prevalence of such mutations as well as by testing for these events in other tissues; most genetic investigations are performed only in blood, so we may have missed some disease-causing mutations by not testing elsewhere,” Dr Gilissen will conclude.


Abstract no:  C02.6

The work was partially funded by the Netherlands Organisation for Scientific Research and the European Research Council.

ASHG and ESHG Issue Position Statement on Non-Invasive Prenatal Screening

For Immediate Release
Tuesday, March 25, 2015
16:00 hrs CET

BETHESDA, MD, USA and VIENNA, AUSTRIA – Two of the world’s largest professional societies of human geneticists have issued a joint position statement on the promise and challenges of non-invasive prenatal testing (NIPT), a new procedure to test blood drawn from pregnant mothers for Down syndrome and other chromosomal disorders in the fetus. The document addresses the current scope of and likely future improvements in NIPT technology, ways it may best fit with existing prenatal screening tools and protocols, options and priorities in its implementation, and associated social and ethical issues.

The statement, drafted by the Social Issues Committee of the American Society of Human Genetics (ASHG) and the Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), was published online March 18 in the European Journal of Human Genetics.

Current prenatal screening protocols for common structural abnormalities in the chromosomes vary among countries and medical practices. Generally, though, pregnant women are offered a combined first-trimester screening (cFTS), a risk assessment test based on blood and ultrasound markers. Women who receive abnormal cFTS results undergo a second step of testing to confirm or deny whether the fetus has a chromosomal abnormality such as Down syndrome. This second step involves invasive procedures, such as amniocentesis, that in 0.5-1% of cases may lead to a miscarriage.

One important drawback of cFTS is the high rate of false alarms that lead to invasive procedures that put pregnancies at risk when the fetus is actually chromosomally normal. The main benefit of NIPT, apart from a significantly higher detection rate, is that it dramatically lowers the false alarm rate from about 5% to about 0.2%, making prenatal screening more accurate and safe. This is achieved by analyzing fragments of DNA in maternal blood, some of which provides information about the fetus. The fact that this ‘fetal DNA’ actually derives from the placenta is one reason why NIPT is not fully reliable. An important implication of this is that women who receive an abnormal NIPT result should still be advised to confirm this result through a second step of testing if they are considering a termination of pregnancy, the statement authors write.

The authors explored the benefits and drawbacks of various ways to implement NIPT, such as adding it to the current two-step process or using it to replace cFTS. As NIPT is significantly more expensive, the cost per test would need to be reduced considerably for the latter option to be feasible in fully funded prenatal screening programs, they noted. They also considered implications of the technology, including pressures on women to undergo the test and act upon the results, and the loss of ultrasound data that would indicate fetal problems if that step is removed from the screening process.

“Throughout our discussion, we kept in mind that the goal of prenatal screening is to enable autonomous, informed reproductive choices by pregnant women and their partners, not to prevent the birth of children with specific abnormalities,” said Yvonne Bombard, PhD, 2014 chair of the ASHG Social Issues Committee.

The two committees also addressed emerging advances in NIPT technology that would allow testing for additional genetic conditions, such as rare microdeletion syndromes and syndromes that interfere with sexual development. They noted that as NIPT grows to include more conditions – producing results of varying certainty – pre-test genetic counseling will become significantly more complex.

“We are concerned about prematurely expanding NIPT beyond Down syndrome and a few other chromosomal abnormalities to include rare conditions for which it may not be sufficiently validated, or of which the clinical implications may not be fully understood. For example, parents-to-be will have to make difficult choices about how to act upon abnormal results for such conditions,” said Wybo Dondorp, PhD, first author of the statement.

“A related concern about prematurely expanding the scope of the test is that it will reverse the significant decrease in false alarms and subsequent need for follow-up diagnostic procedures, which has been regarded as the main gain of NIPT in prenatal screening,” said Diana Bianchi, MD, a member of the ASHG Social Issues Committee and co-author on the statement.

The statement authors also considered the longer-term question of how extensive prenatal genetic screening should be, and emphasized the role of infrastructure in enabling responsible use of NIPT. Priorities included educating health professionals and the public about its benefits and limitations, promoting equal access despite cost issues, controlling the quality of pre-test counseling and laboratory practices, and systematically evaluating the whole process. In all, the two committees published ten recommendations for the broader implementation of NIPT, including suggested next steps.

“We are excited about the potential of NIPT to produce more accurate results and reduce the need for invasive testing,” said Martina Cornel, MD, PhD, chair of the ESHG Public and Professional Policy Committee. “However, in view of its future potential, the responsible introduction and expansion of this technology remains an important challenge. In countries where prenatal screening is offered as a public health service, governments and public health authorities should take a more active role in this regard.”

Resource: W Dondorp et al. (epub 2015 Mar 18). Non-invasive prenatal testing for aneuploidy and beyond: Challenges of responsible innovation in prenatal screening. European Journal of Human Genetics. DOI: 10.1038/ejhg.2015.57


About the European Society of Human Genetics (ESHG)

The European Society of Human Genetics is a non-profit organization. Founded in 1967, its aims are to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. The Society encourages and seeks to integrate research and its translation into clinical benefits and professional and public education in all areas of human genetics.  


About the American Society of Human Genetics (ASHG)

Founded in 1948, the American Society of Human Genetics is the primary professional membership organization for human genetics specialists worldwide. Its nearly 8,000 members include researchers, academicians, clinicians, laboratory practice professionals, genetic counselors, nurses, and others with an interest in human genetics. The Society serves scientists, health professionals, and the public by providing forums to: (1) share research results through the ASHG Annual Meeting and in The American Journal of Human Genetics; (2) advance genetic research by advocating for research support; (3) educate current and future genetics professionals, health care providers, advocates, policymakers, educators, students, and the public about all aspects of human genetics; and (4) promote genetic services and support responsible social and scientific policies. For more information, visit:



Proposed amendments to EU Regulation on Medical Devices are counter to patients’ interests and unworkable, says ESHG

Recent amendments to the proposed Regulation on In Vitro Diagnostic Medical Devices (IVDs) currently before the European Parliament will restrict the rights of patients and doctors to carry out essential genetic testing, says the European Society of Human Genetics (ESHG) today (Monday 7 April 2014). Furthermore, an independent legal opinion now shows that the European Union (EU) has no competence to enact the Regulation as amended by the Parliament.

More information.

ESHG 2014, Milan - Uncovering deletions and duplications in the exome can help pinpoint cause of unexplained genetic diseases

Embargo: 00.01 hrs CEST Monday 2 June 2014

Milan, Italy:   Analysis of genetic variation in the exome, the DNA sequence of genes that are translated into protein, can aid in uncovering the cause of conditions for which no genetic cause could previously be found, and this can directly impact clinical management, the annual conference of the European Society of Human Genetics will hear today.  Dr Jayne Hehir-Kwa, Assistant Professor of Bioinformatics in the Translational Research group, Department of Human Genetics, Radboud UMC, Nijmegen, The Netherlands, will describe results from her group’s study that set out to determine whether copy number variants (CNVs), large genomic deletions or duplications, can contribute to diseases other than intellectual disability.

The role of CNVs in intellectual disability is well known, but their implication in other conditions is less so. “There are, for example, case reports describing deletions in blindness, but no-one has determined the full extent of CNVs in other patient groups,” Dr Hehir-Kwa will say.

The team screened 600 patients for which no diagnosis or causal mutation could be found using current whole exome sequencing (WES) methodology, and looked genome-wide for a causal deletion or duplication.  It is, they say, the first time anyone has screened systematically for a disease mechanism in such a large and diverse patient group, including five heterogeneous conditions – intellectual disability, deafness, blindness, metabolic disorders, and movement disorders.

“For these patient groups, targeted gene approaches have been traditionally used for mutation screening and hence the contribution of CNVs to these disease groups has never been established and genome-wide testing rarely applied,” says Dr Hehir-Kwa. “Our results show that CNVs are a relatively common, clinically-relevant event.”

CNVs were found in patients with many different kinds of disorders, for example retinitis pigmentosa (blindness), Usher syndrome (deafness), Bethlem/Ulrich myopathy (a congenital form of muscular dystrophy), hypotonia-cystinuria syndrome (a neonatal-onset metabolic disorder) and X-linked immunodeficiency (an inherited disorder of the immune system).

“Although WES is not perfect in terms of completely cataloguing genomic variation, our work has shown that it can play an important part in diagnosis. In addition to helping us devise better clinical management strategies for patients, it also affects their prognosis and provides information which can aid us with reproductive counselling for affected individuals,” says Dr Hehir-Kwa. “As a result, we are now offering the CNV screening performed in our study as a standard diagnostic procedure in exome analysis for patients where the genetic cause of their condition has not been found previously.”

The diagnostic yield differs between the different disease categories, the researchers say. Traditional screening for genetic mutations can explain 27% of intellectual disability, 52% of blindness, and up to 20% of individuals with mitochondrial and movement disorders.  “This means that between 48-80% of patients screened with WES are not given a genetic diagnosis.  By looking for CNVs in the exon regions of these undiagnosed patients we estimate that we can find such a diagnosis in about a further four percent. In particular, the blindness conditions seem to have the highest yield of CNVs – up to seven percent,” says Dr Hehir-Kwa. “I would like to see screening for more types of genomic variants become standard procedure in genetic diagnostics. The genome of an individual can contain all kinds of different variants, in all shapes and sizes, and it is important that we take all these variations into account.”

WES, when offered as a first tier diagnostic test, can give a high diagnostic yield, and the result is faster diagnostics at lower cost. “The more complete and thorough we can make such a diagnostic test, the more accessible we make genetic testing for the public. However clinical health care professionals need to be well informed about the different genetic disease mechanisms to provide the best possible counselling for patients,” Dr Hehir-Kwa will conclude.


Abstract no:  P14.80/M

Note:   When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.

Notes to editors:  The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe.   It currently has about 2000 members from 72 countries.   About 3000 delegates are expected to attend this year’s conference.

ESHG 2014, Milan - Discovery of new genes involved in food preferences will revolutionise diets and improve health

Embargo: 00.01 hrs CEST Monday 2 June 2014

Milan, Italy:  New understanding of the genes involved in taste perception and food preferences could lead to personalised nutrition plans effective not just in weight loss but in avoiding  diseases such as cancer, depression, and hypertension, Italian researchers will tell the annual conference of the European Society of Human Genetics (ESHG) today (Monday).   Knowing why individuals prefer certain food tastes and being able to personalise health interventions based on them will help people age in a healthier way and greatly improve their quality of life, as well as engender considerable savings for health systems, they say.

Dr Nicola Pirastu and Dr Antonietta Robino, from the University of Trieste and the IRCCS Burlo Garofolo Institute for Maternal and Child Health, Trieste, Italy, set out to identify novel genes and pathways involved in taste perception and food preferences, and to investigate their implications in protecting against or predisposing to diet-related disorders such as overweight, obesity, and diabetes.  “To date most studies have focused on specific taste receptors, especially bitter ones, and this has been partly successful in an attempt to understand the genetics behind the perception of specific compounds such as caffeine and quinine,” says Dr Robino. “Our work has expanded these studies to the whole genome, with the goal of clarifying which specific genes drive individual differences in taste perception and food preferences.”

The researchers undertook genome wide association studies (GWAS) to try to unravel the genetic basis for certain food preferences.  2311 Italian subjects participated in the discovery step, while 1755 from other European countries and from Central Asia were used in order to further verify the findings.  They uncovered 17 independent genes related to liking for certain foods, including artichokes, bacon, coffee, chicory, dark chocolate, blue cheese, ice cream, liver, oil or butter on bread, orange juice, plain yoghurt, white wine and mushrooms.  Surprisingly, none of the genes thus identified belonged to the category of taste or smell receptors.

“There is still much that needs to be done to understand what are the characteristics of certain foods affected by the genetic make-up of an individual,” says Dr Pirastu.  “For example, we found a strong correlation between the HLA-DOA gene and white wine liking, but we have no idea which of the characteristics of white wine this gene influences. Our studies will be important for understanding the interaction between the environment, lifestyles, and the genome in determining health outcomes. Although there has been a lot of work on food-related diseases such as obesity, these have rarely taken food preferences into account.  This is a major limitation which our work attempts to remedy, and as yet we have only really scratched the surface of this issue.”

In a second study, the researchers amassed the response of around 900 healthy adults from North Eastern Italy to salt, and related this to a DNA sequence variation found on the KCNA5 gene, known to be related to taste pathways in mammals.  Salt perception and the related genetic variation in taste receptors are important determinants of individual differences in salt intake, which in turn represents an important risk factor for the development of hypertension and cardiovascular diseases. “Genetic variations for taste perception are well known for bitter, sweet, and umami taste, but until now we knew little about their role in salt perception and liking,” says Dr Robino. “Identifying the receptor associated with individual differences in the perception of salt could help us better understand how chemosensory differences can interact to influence and predict food choices and hence human nutritional behaviour.  This could also play an important role in the development of salt substitutes, in which there is a growing commercial interest.”

Nutritional intervention could be greatly improved by tailoring it to the food preferences of each person, the researchers say.  And food preferences are also much easier to collect and study; while it is almost impossible to remember much one has eaten in the past ten years, it is easy to remember food likes and dislikes.

“By uncovering the genetic bases of taste and food preferences, we will be able to increase not only the effectiveness of nutritional interventions, but also compliance with them. For example, we have recently carried out a study where we applied our knowledge of 19 different genes in order to personalise diets for 191 obese individuals for were trying to lose weight.  They were divided into two groups, 87 in a test group and 104 controls,” says Dr Pirastu.

“We devised a standard weight-loss diet subtracting 600 calories from individual nutritional needs, and analysed DNA from the test group for 19 genes known to affect different metabolic areas and taste.  We then modulated the diets according to individual genetic profiles – for example, people whose genetic profile showed that they had less efficient lipid metabolism were given fewer lipids in their diet – but kept the overall amount of calories the same for everyone.

“Although there were no significant differences in age, sex and BMI between the two groups at the beginning of the trial, we found that people in the group who had followed the gene-based diet lost 33% more weight than the controls over two years, and the percentage of lean body mass also increased more in this group,” he will say.

Food preferences are the first factor driving food choice, nutrition and ultimately diet-related diseases and as such are the key to understanding human nutrition and its relationship with health on a large scale, the researchers say.  A recent study1 carried out on more than 40,000 people showed that people who prefer fat have a completely different eating pattern than people who dislike it. “So something as simple as measuring fat liking can provide us with a great deal of information.  Understanding the genetics of these traits will open new possibilities for the development of personalised diets and of functional foods aimed at improving people’s health and therefore their quality of life,” Dr Pirastu will conclude.

Abstract nos. C14.3, P17.26-M, and P15.19-S

1. Association between intake of nutrients and food groups and liking for fat, Caroline Mèjean et al. Appetite, 2014

Note:   When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.

Notes to editors:  The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe.   It currently has about 2000 members from 72 countries.   About 3000 delegates are expected to attend this year’s conference.

ESHG 2014, Milan - Poor coverage of specific gene sets in exome sequencing give cause for concern

Embargo: 00.01hrs CEST Sunday 1 June 2014

Milan, Italy: With services based on exome sequencing becoming affordable to patients at a reasonable price, the question of the quality of the results provided has become increasingly important. The exome is the DNA sequence of genes that are translated into protein. These protein-coding regions contain most of the currently-known disease-causing genetic mutations. The American College of Medical Genetics and Genomics (ACMG) has recommended the reporting to patients of clinically actionable incidental genetic findings in the course of clinical exome testing. Specifically, mutations of 56 specific genes with known clinical importance should be reported even when they are incidental to the patient’s current medical condition.  However, a new study to be reported to the annual conference of the European Society of Human Genetics (ESHG) today (Sunday) shows that exome sequencing, as currently performed, does not always produce high quality results when examining subsets of genes such as the 56 ACMG genes.

Dr Eric Londin1, Assistant Professor in the Computational Medicine Centre, Department of Pathology, Anatomy and Cellular Biology, Thomas Jefferson University, Philadelphia, USA, will tell the conference that analysis of 44 exome datasets from four different testing kits showed that they missed a high proportion of clinically relevant regions in the 56 ACMG genes. “At least one gene in each exome method was missing more than 40 percent of disease-causing genetic variants, and we found that the worst-performing method missed more than 90 percent of such variants in four of the 56 genes,” he says.

A central question, the researchers say, is not how often a clinical diagnosis can be made using exome sequencing, but how often it is missed, and the study shows clearly that there is a high false-negative rate using existing sequencing kits.  “Our concern is that when a clinical exome analysis does not report a disease-causing genetic variant, it may be rather that the location of that variant has not been analysed rather than the patient’s DNA being free of a disease-causing variant,” says Dr Londin. “Depending on the method and the laboratory, a significant fraction (more than ten percent) of the exome may be untested and this raises concerns as to how results are being communicated to patients and their families. “

A total of 17,774 disease-causing genetic variants are annotated in the Human Gene Mutation Database (HGMD) for the 56 genes mentioned in the ACMG recommendations. The researchers examined the coverage of the exome datasets for the locations where the 17,774 disease-causing variants can occur.  Although the exome datasets are comparable in quality to other published clinical and research exome data sets, the coverage of the disease-causing locations was very heterogeneous and often poor.  The researchers believe that clinical laboratories that implement the ACMG reporting guidelines should recognise the substantial possibility of reporting false negative results.

One potential improvement would be to have clinical exome sequencing use methods designed to provide a maximum yield of all clinically relevant genes. “Many of the currently used exome kits are designed to provide a very broad dataset including genomic features that do not yet have a well-established clinical association. There is a need to develop new kits and methods which provide adequate and reliable coverage of genes with known disease associations. If adequate performance cannot be obtained across the exome, then further use of targeted disease-specific panels of genes should be explored,” Dr. Londin says.

The study also found that exome datasets generated from low amounts of sequence data (fewer than six gigabases) performed much worse than datasets that were generated from higher amounts of sequence data (more than ten gigabases). This finding is consistent with previous studies showing that exome methods do not have a linear relationship between sequence-generated and nucleotide2 coverage. Instead, a minimum threshold of sequencing data needs to be met before optimum nucleotide coverage is obtained.

“Current consensus and regulatory guidelines do not prescribe a minimum data requirement for clinical exome tests. The result is that when a causative variant cannot be identified it does not necessarily imply that the variant is not present, rather that there may be a technical issue with the exome technology used.  In other words, a clinical ‘whole exome’ study may not be ‘wholesome’ in coverage.  Patients and their families should be made aware of this problem and of the implications of the genomic findings of clinical exome sequencing in its current state,” Dr. Londin will conclude. (ends)

1. In collaboration with Dr Jason Park at the University of Texas Southwestern Medical Center and Children’s Medical Center, Dallas, Drs. Larry Kricka at University of Pennsylvania, Dr Marialuisa Sponziello at the University Sapienza, Rome, Dr Peter Clark at the Children’s Hospital of Philadelphia and Dr Paolo Fortina at the Kimmel Cancer Center of Thomas Jefferson University.

2.Nucleotides are the subunit molecules of DNA

Funding: This work was supported in part by the Kimmel Cancer Center (PF), the Computational Medicine Center (ER), by a grant from Sapienza University of Rome (MS).

Abstract no. C07.6

Note:   When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.

Notes to editors:  The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe.   It currently has about 2000 members from 72 countries.   About 3000 delegates are expected to attend this year’s conference.

ESHG 2014, Milan - Genetic researchers take a major step towards better diagnosis and treatment of osteoporosis

Embargo: 00.01hrs Sunday 1 June 2014

Milan, Italy: A new target that may be critical for the treatment of osteoporosis, a disease which affects about 25% of post-menopausal women, has been discovered by a group of researchers in The Netherlands and in Germany. Professor Brunhilde Wirth, Head of the Institute of Human Genetics, University of Cologne, Germany, will tell the annual conference of the European Society of Human Genetics tomorrow (Sunday) that new studies in zebrafish and mice have shown that either injection of human plastin 3 (PLS3) or related proteins in zebrafish where PLS3 action has been suppressed can replace its loss and repair the bone development anomalies associated with this deficiency. Furthermore, overexpression of human (PLS3) in normal mice had a significant impact on bone development and maintenance making them more resistant to fractures.

The discovery that PLS3 mutations could cause osteoporosis was published last year in The New England Journal of Medicine. 1 The results came as a surprise to the researchers, since mutations in the PLS3 gene had not previously been known to be related to osteoporosis and fractures, or to play a role in bone formation. “In our most recent research, we started out by using zebrafish embryos in which PLS3 was knocked-out and studying their development at the three and five day-old stage,” says Professor Wirth, “and we found that they had massive impairment of craniofacial skeletal development. However, this was fully restored when we added human PLS3. The same thing happened when we added two other proteins, actinin 1 and actinin 4, F-actin proteins2 which are involved in ‘bundling’ or building the ‘scaffolding’ for cells, and it seems that these proteins can compensate for the loss of PLS3.  Thus we have been able to verify the essential role of actin in bone development and maintenance.”

The subsequent mouse studies confirmed the findings in zebrafish, the researchers say, and open up possibilities for new treatments. They now intend to use PLS3 knock-out mice, where the PLS3 gene has been removed, in the search for the disease-causing mechanism involved.  PLS3 is expressed in three different types of cells - osteocytes and osteoclasts, both involved in bone growth and remodelling, as well as in muscle cells.  Using a transgenic mouse that overexpresses PLS3, they will also investigate whether this overexpression could be effective in other diseases involving in bone weakness.

“Since we know that about five percent of the human population expresses higher than normal levels of PLS3, we can hypothesise that these people may be protected against osteoporosis,” says Professor Wirth.

Once the researchers understand the exact disease-causing mechanism, it may be possible to translate the knowledge into therapy, they say. PLS3 overexpression is also protective against spinal muscular atrophy, the second most frequent autosomal recessive disorder in humans.3 This implies that understanding the protective role of PLS3 is crucial in both disorders. “We are currently trying to unravel the whole protein network and, once we have understood the signalling pathways influencing PLS3 expression, we should be able to identify drugs or molecules that influence PLS3 expression or actin proteins,” she says.

Osteoporosis affects not only post-menopausal women, but also older men, and the condition currently causes more than 8.9 million fractures per year or an osteoporitic fracture every three seconds. Worldwide one in three women over 50 will experience fractures due to osteoporosis, as will one in five men. Currently, emphasis for sufferers is on the prevention of falls that can cause broken bones. Although bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained an osteoporotic fracture, they are otherwise of little use.

“Osteoporosis poses an urgent health problem that is going to become more important as years go with the numbers of elderly people in the community continuing to increase,” says Professor Wirth.  “Although in itself it is not a fatal illness, large numbers of people die prematurely as a result of health complications following falls. We believe that our work has led to a better understanding of the condition and has pointed the way towards improved diagnosis and prevention, and, we hope, an effective treatment in the future.”


1.N Engl J Med 2013; 369:1529-1536 DOI: 10.1056

2.F-actin is a multi-functional filamentous protein essential for regulating the mobility and contraction of cells.

3.An autosomal recessive disorder is one where two copies of an abnormal gene must be present in order to the disease or condition to develop.

Abstract no. C10.2

Note:   When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.

Notes to editors:  The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe.   It currently has about 2000 members from 72 countries.   About 3000 delegates are expected to attend this year’s conference.

ESHG 2014, Milan - New genetic sequencing methods mean quicker, cheaper, and equally accurate embryo screening

Embargo: 00.01 hrs CEST Saturday 31 May 2014

Milan, Italy: Results from the first study of the clinical application of next generation DNA sequencing (NGS) in screening embryos for genetic disease prior to implantation in patients undergoing in-vitro fertilisation treatments show that it is an effective reliable method of selecting the best embryos to transfer, the annual conference of the European Society of Human Genetics will hear tomorrow (Sunday).  Dr Francesco Fiorentino, from the GENOMA Molecular Genetics Laboratory, Rome, Italy, will say that his team’s research has shown that NGS, a high throughput sequencing method, has the potential to revolutionise pre-implantation genetic screening (PGS).  The technique can result in reduced cost, faster results, and accurate identification of good embryos resulting in more ongoing pregnancies, he will say.

The researchers undertook a prospective, double blind trial using two methods of embryo screening, NGS, and the older method array-comparative genomic hybridisation (Array-CGH) of 192 blastocysts, or early embryos, obtained from 55 consecutive clinical pre-implantation genetic screening (PGS) cycles.  Array-CGH was the first technology to be widely available for the accurate analysis of chromosomal abnormalities in the embryo and is used extensively across the world for this purpose.

Fifty five patients with an average age of 40 years were enrolled; in 45 cases they were undertaking IVF because of advanced age and in ten because of repeated IVF failures.  Two different teams of researchers carried out biopsies and analysed the genetic make-up of the embryos at between five and six/seven days, depending on the speed of growth, and then measured the consistency of the diagnosis by comparing results from the two sequencing methods.

This comparison showed concordant results for 191 of the 192 embryos analysed.  One embryo showed a false positive for three copies of chromosome 22 (trisomy 22) using the NGS technique.  But analysis of this embryo also showed concordance between the two methods in detecting several other chromosomal abnormalities, and it would therefore have been ruled for transfer in any event. There were no other false negative diagnoses for chromosome abnormalities, and no inaccurate predictions of gender.  NGS also showed itself to be as capable of identifying small, difficult to detect abnormalities.

 “We found that results from the NGS and array-CGH diagnostic tests were highly concordant,” Dr Fiorentino will say.  “NGS allowed us to detect a number of different abnormalities in 4608 chromosomes with a very high degree of accuracy, and following the transfer of 50 healthy embryos in 46 women, 30 pregnancies continued.”

These pregnancies were confirmed by the presence of a foetal sac and a heartbeat, and all have now completed at last 20 weeks of gestation.

PGS has been the subject of controversy over recent years.  Initially hailed as an opportunity to improve clinical outcome in sub-fertile patients undergoing IVF, a number of studies later appeared to show that it might not help to identify and select chromosomally normal embryos for transfer based on its lack of benefit with respect to improving life birth rates.

 “However, these studies used an older screening technique, fluorescent in-situ hybridisation (FISH),” says Dr Fiorentino, “and we hypothesised that NGS might come up with more accurate results.  The results of our study have proved this to be the case, and that NGS can improve clinical outcomes. We expect that the use of NGS technologies will increase as evidence of their utility becomes better-known.

“A further advantage of the technique is that it is quicker and cheaper, while remaining just as sensitive as other methods of screening.  Our next step will be to participate in a large randomised controlled trial, the results of which will be critical for the acceptance of NGS-based pre-implantation embryo assessment into wider clinical practice.”

Abstract no:  P01.023/S

Note:   When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.

Notes to editors:  The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe.   It currently has about 2000 members from 72 countries.   About 3000 delegates are expected to attend this year’s conference.

Proposed amendments to EU Regulation on Medical Devices are counter to patients’ interests and unworkable, says ESHG

Recent amendments to the proposed Regulation on In Vitro Diagnostic Medical Devices (IVDs) currently before the European Parliament will restrict the rights of patients and doctors to carry out essential genetic testing, says the European Society of Human Genetics (ESHG) today (Monday 7 April 2014). Furthermore, an independent legal opinion now shows that the European Union (EU) has no competence to enact the Regulation as amended by the Parliament.

More information


European Society of Human Genetics urges caution over use of new genetic sequencing techniques

The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease.  However, it can also pose major ethical problems if used incorrectly, say new recommendations from the European Society of Human Genetics (ESHG) published on line today (16 May 2013) in the European Journal of Human Genetics ( 

Many services based on whole genome and on exome* sequencing and analysis are now available to patients at an affordable price, and this raises the question of how to ensure that they are provided appropriately.  “Such sequencing generates huge amounts of information that needs to be processed, analysed, and stored in a responsible manner”, said Professor Martina Cornel, chair of the Professional and Public Policy Committee of ESHG. “It is preferable to use sequencing or analysis specifically targeted at a particular health problem to avoid unsolicited findings, or those that cannot yet be interpreted, which can cause considerable anxiety to patients and their families.  Clear guidance on how to deal with such findings is needed.

”Targeted analysis will limit such unsolicited findings, says the ESHG, and this is particularly important at present when there are only a limited number of clinicians properly trained to inform patients on the significance of the results of GWAs and exome sequencing.  While the Society believes that the duty to inform patients may outweigh their right not to know in some circumstances, the new recommendations propose that analysis should be limited to genome regions linked to the clinical problem for which the analysis is being undertaken.  

“We are opposed to the type of opportunistic screening that throws up large numbers of incidental results.  If such results reveal a treatable or preventable condition, then clearly it is advantageous to patients to be informed about them.  But in the majority of cases it is very difficult to interpret exactly what such incidental results mean for patients and their families. The evidence currently available often comes from families with affected persons, but it is lacking on the interpretation of results in other situations. Furthermore, in genetics healthcare, autonomy is considered very important: patients should be allowed consent on what would be screened for and reported to them. We believe that it is premature today to look for such results other than the clinical problem in circumstances where there are no prior clinical indications or family history ”, said Professor Cornel.

“A sustained effort to educate clinicians in genetics is needed in order to be able to cope with advances in analysis.   We also believe that the Society has an important role to play in raising awareness of genetics among the general public.  Only with the benefit of a general increase in genetic literacy can society become properly involved in the debate over who has the right to know what and in which circumstances,” she said.

Professor GertJan van Ommen, Editor in Chief of the European Journal of Human Genetics, said: “The importance of this issue has been underlined by the US Government's Bioethics Advisory Panel's plans to report on how incidental findings encountered in genomics research should be handled.  I believe that ESHG has made an important contribution to the debate, which will be further discussed at their conference in Paris in June.”


*Exomes are the short sequences of DNA representing the regions in genes that are translated into protein


Privately owned genetic databases may hinder diagnosis and bar the way to the arrival of personalised medicine: ESHG reacts to today's report in the European Journal of Human Genetics

Wednesday, October 31, 2012

In response to the on-line publication by the European Journal of Human Genetics today (Wednesday) of an article by US researchers led by Dr. Robert Cook-Degan, a former member of the US Office of Technology Assessment, showing that Myriad Genetics, providers of the BRCA1/2 genetic test in the US, has amassed vast quantities of clinical data without sharing it, Professor Martina Cornel, chair of the European Society of Human Genetics' Professional and Public Policy committee, said:

“We are very concerned that such important data is being withheld from those who most need it. Interpreting the variants of unknown significance (VUS) that may be found on analysing the patient's genome plays an essential part in being able to provide proper counselling and if necessary, preventive or therapeutic guidance. By not sharing their data on the VUS obtained from individuals undergoing BRCA1/2 testing, where Myriad is the sole commercial provider of a test in the US, geneticists have been unable to develop the up-to-date algorithms that are necessary to best interpret the effects of genetic variants. While Myriad has access to public databases in order to help interpret their VUS results, this is currently not reciprocal.

“We know that, regrettably, medical geographic inequities are common, but what is particularly worrying about this situation is that it is the first time that such inequities have been based on a lack of access to clinical information, rather than lack of a product. Myriad's stated aim to enter the European market more vigorously may lead to unfair competition with academic institutions for predictive precision. It is vital that progress towards personalised medicine, which holds out so much promise, is not hindered by companies maintaining private genomic databases. Policymakers should take an urgent look at the regulatory and reimbursement issues involved in genomic testing in order for all the data that is essential to understanding the clinical significance of VUS to be made public, to the benefit of patients and healthcare providers alike.”

View the paper

ESHG condemns use of testing to establish 'racial purity'

Wednesday, June 13, 2012

The use of genetic testing to establish racial origins for political purposes is not only scientifically foolish, but also unethical and should be condemned, the European Society of Human Genetics (ESHG) said today (Thursday June 14).   The society, which promotes research in basic and applied human and medical genetics and ensures high standards in clinical genetic practice, said that the use by a member of parliament from the Hungarian far-right Jobbik party of a genetic test to attempt to prove his ”˜ethnic purity' was ethically unacceptable.

The company Nagy Gén scanned 18 positions in the MP's genome for variants that it said were characteristic of Roma and Jewish ethnic groups and concluded that Roma and Jewish ancestry could be ruled out.

Professor Joerg Schmidtke, President of ESHG, said on behalf of the Executive Board:  “This is a gross distortion of the values of genetic testing, which is intended to be used to diagnose disease rather than to claim racial purity.  In addition, the test proves nothing; it is impossible to deduce someone's origins from testing so few places in the genome.  I am sure that clinical geneticists worldwide will join me in condemning this scandalous abuse of a technology that was developed to help the sick, rather than to promote hatred.”

Professor Béla Melegh, President of the Hungarian Society of Human Genetics added: “We were shocked to hear that a laboratory authorised to carry out genetic analysis for diagnostic purposes carried out such a test.  Not only does it not serve a diagnostic purpose, but it has been used to create tension between people of different ethnic origins.  We are asking the Hungarian government to prosecute the company concerned under the 2008 law on genetics, and to take action to ensure that similar abuse of genetic testing cannot take place in our country in future.”

The 2012 European Genetics Conferences in Nuremberg, Germany (June 23-26) will provide a further opportunity for the ESHG to denounce such an unethical perversion of genetic science, and insist, at the same time, on the importance of genetic testing in the medical or scientific context of good practice.

Privately owned genetic databases may hinder diagnosis and bar the way to the arrival of personalised medicine: ESHG reacts to the report in the European Journal of Human Genetics

In response to the on-line publication by the European Journal of Human Genetics today (Wednesday) of an article by US researchers led by Dr. Robert Cook-Degan, a former member of the US Office of Technology Assessment, showing that Myriad Genetics, providers of the BRCA1/2 genetic test in the US, has amassed vast quantities of clinical data without sharing it, Professor Martina Cornel, chair of the European Society of Human Genetics' Professional and Public Policy committee, said:

“We are very concerned that such important data is being withheld from those who most need it. Interpreting the variants of unknown significance (VUS) that may be found on analysing the patient's genome plays an essential part in being able to provide proper counselling and if necessary, preventive or therapeutic guidance. By not sharing their data on the VUS obtained from individuals undergoing BRCA1/2 testing, where Myriad is the sole commercial provider of a test in the US, geneticists have been unable to develop the up-to-date algorithms that are necessary to best interpret the effects of genetic variants. While Myriad has access to public databases in order to help interpret their VUS results, this is currently not reciprocal.

“We know that, regrettably, medical geographic inequities are common, but what is particularly worrying about this situation is that it is the first time that such inequities have been based on a lack of access to clinical information, rather than lack of a product. Myriad's stated aim to enter the European market more vigorously may lead to unfair competition with academic institutions for predictive precision. It is vital that progress towards personalised medicine, which holds out so much promise, is not hindered by companies maintaining private genomic databases. Policymakers should take an urgent look at the regulatory and reimbursement issues involved in genomic testing in order for all the data that is essential to understanding the clinical significance of VUS to be made public, to the benefit of patients and healthcare providers alike.”


Annual Meeting 2010
June 12, 2010


Annual Meeting 2009
May 25, 2009

Opposites attract - how genetics influences humans to choose their mates

Vienna, Austria: New light has been thrown on how humans choose their partners, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday May 25). Professor Maria da Graça Bicalho, head of the Immunogenetics and Histocompatibility Laboratory at the University of Parana, Brazil, says that her research had shown that people with diverse major histocompatibility complexes (MHCs) were more likely to choose each other as mates than those whose MHCs were similar, and that this was likely to be an evolutionary strategy to ensure healthy reproduction.


Scientists find shared genetic link between the dental disease periodontitis and heart attack

Vienna, Austria: The relationship between the dental disease periodontitis and coronary heart disease (CHD) has been known for several years. Although a genetic link seemed likely, until now its existence was uncertain. Now, for the first time, scientists have discovered a genetic relationship between the two conditions, a researcher told the annual conference of the European Society of Human Genetics today (Monday 25 May).


Identification of genetic variants affecting age at menopause could help improve fertility treatment

Vienna, Austria: For the first time, scientists have been able to identify genetic factors that influence the age at which natural menopause occurs in women. Ms Lisette Stolk, a researcher from Erasmus MC, Rotterdam, The Netherlands, told the annual conference of the European Society of Human Genetics today ( Monday 25 May) that a greater understanding of the factors influencing age at menopause might eventually help to improve the clinical treatment of infertile women.


Comprehensive cardiogenetic testing for families of sudden unexplained death victims can save lives, scientists say

Vienna, Austria: Relatives of a young person who dies suddenly should always be referred for cardiological and genetic examination in order to identify if they too are at risk of sudden death, a scientist told the annual conference of the European Society of Human Genetics today (Tuesday 26 May). Dr. Christian van der Werf, a research fellow at the Department of Cardiogenetics, Academic Medical Centre, Amsterdam, The Netherlands said that, although his team's research showed that inherited heart disease was present in over 30% of the families of sudden unexplained death (SUD) victims, the majority of such relatives were currently not being referred for examination.



Annual Meeting 2008
June 3, 2008

Greater awareness of genetic testing possibilities for impaired fetal movement can save babies' lives

Barcelona, Spain: New genetic mutations responsible for impaired fetal movement, which leads to a multitude or problems in later life as well as early spontaneous abortion, have been identified by a group of scientists, the annual conference of the European Society of Human Genetics will hear today (Saturday 31 May). Dr. Katrin Hoffmann, of the Charité University Hospital, Berlin, Germany, will say that her team's findings could lead to strategies to prevent multiple miscarriages, and for children born with fetal akinesia deformation sequence (FADS) due to impaired fetal movement in the womb.


Genetic mutation linked to walking on all fours: discovery could help answer basic questions of upright walking

Barcelona, Spain: What are the genes implicated in upright walking of humans? The discovery of four families in which some members only walk on all fours (quadrupedality) may help us understand how humans, unlike other primates, are able to walk for long periods on only two legs, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday 2 June).

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Prenatal biochemical screening only detects half of chromosomal abnormalities; women should be better informed before deciding to undertake it

Barcelona, Spain: Prenatal biochemical screening tests are widely used to look for chromosomal abnormalities in the fetus which can lead to serious handicap, or even death during gestation or in the first few days after birth. But these tests are only able to detect fewer than half of the total chromosomal abnormalities in the fetus, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday 2 June) Dr. Francesca R. Grati, of the TOMA Laboratory, Busto Arsizio, Italy, says that these findings mean that women should be better informed on the limitations of such diagnostic tests.

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Gene therapy involving antibiotics may help patients with Usher syndrome

Barcelona, Spain: A new approach to treating vision loss caused by Type 1 Usher syndrome (USH1), the most common condition affecting both sight and hearing, will be unveiled by a scientist at the annual conference of the European Society of Human Genetics today (Tuesday 3 June). Ms Annie Rebibo Sabbah, from the Genetics Department of the Rappaport Faculty of Medicine, Technion, Haifa, Isreal, will tell the conference that preliminary results using a class of drugs called aminoglycosides, commonly used as antibiotics, had had promising effects in vitro and in cell culture.

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Discovery of new family of genetic mutations brings hope of better treatment for patients with inflammatory intestinal disease

Barcelona, Spain: The discovery of new genetic mutations involved in inflammatory intestinal disorders could lead to a better understanding of these common conditions, two scientists told the annual conference of the European Society of Human Genetics today (Monday 2 June).



January 10, 2008
ESHG 2007 Abstract Press Release featured in EurekAlert!'s 10 Most Popular Stories in 2007:

"Noninvasive screening in early pregnancy reduces Down's births by 50 percent"
The EurekAlert! 10 Most Popular Stories in 2007 were identified by monitoring Web site traffic and isolating the news releases that received the highest total number of visits between January and December of 2007.

EurekAlert! is an online, global news service operated by the American Association for the Advancement of Science (AAAS). EurekAlert! provides a central place through which learned societies, universities, medical centres, journals, government agencies and other organisations engaged in research can bring their news to the media and the public.

more (pdf document, scroll down to 'Health and Disease Prevention')

Annual Meeting 2007
June 17, 2007

Gene responsible for common hearing loss identified for first time

A gene responsible for the single most common cause of hearing loss among white adults, otosclerosis, has been identified for the first time, a scientist told the annual conference of the European Society of Human Genetics in Nice, France, today (Sunday 17 June). Ms Melissa Thys, from the Department of Medical Genetics, University of Antwerp, Belgium, said that this finding may be a step towards new treatments for otosclerosis, which affects approximately 1 in 250 people.

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Non-invasive screening in early pregnancy reduces Down's births by 50%

Nice, France: Non-invasive screening of pregnant women with ultrasound early in pregnancy, combined with maternal blood analysis, has reduced the number of children born in Denmark with Down Syndrome by 50%, a scientist will tell the annual conference of the European Society of Human Genetics today (Sunday 17 June). Professor Karen Brøndum-Nielsen, of the Kennedy Institute, Glostrup, Denmark, will say that another benefit of the introduction of this procedure in her country was a drop in the number of invasive pre-natal diagnostic procedures from 11% to approx. 6% of pregnancies.


Changes in chromosomal constitution of preimplantation embryos suggest caution in genetic screening

Nice, France: Embryos that are selected out as abnormal can undergo chromosomal modifications, a scientist will tell the annual conference of the European Society of Human Genetics in Nice, France, today (Tuesday 19 June). Ms Tsvia Frumkin, from the Racine IVF unit, LIS Maternity Hospital, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel, will tell the conference that her team's findings meant that the results of preimplantation genetic screening (PGS) for chromosomal abnormalities were not always reliable and should be interpreted with caution.


Children born after PGD as healthy as those born after conventional IVF treatment

Nice, France: Children born after embryo biopsy for preimplantation genetic diagnosis (PGD) do not show any more major malformations than those born after artificial reproduction technologies (ART) without PGD, a scientist will tell the annual conference of the European Society of Human Genetics today (Sunday June 17). Professor Ingeborg Liebaers, from the Research Centre for Reproductive Genetics, Free University of Brussels, Brussels, Belgium, will say that the results of her study of 583 children born after PGD was reassuring.

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Ancient Etruscans were immigrants from Anatolia (now Turkey) - geneticists find the final piece in the puzzle

Nice, France: The long-running controversy about the origins of the Etruscan people appears to be very close to being settled once and for all, a geneticist will tell the annual conference of the European Society of Human Genetics today (Sunday June 17). Professor Alberto Piazza, from the University of Turin, Italy, will say that there is overwhelming evidence that the Etruscans, whose brilliant civilisation flourished 3000 years ago in what is now Tuscany, were settlers from old Anatolia (now in southern Turkey).


Human genetic 'deserts' are teeming with significant life

Nice, France: Many of the areas of the human genome previously thought to be deserts are in fact teeming with life, a scientist will tell the annual conference of the European Society of Human Genetics today (Tuesday 19 June). Most known human genes in the genome map are still incompletely annotated, says Professor Alexandre Reymond, from the Centre for Integrative Genomics, University of Lausanne, Switzerland and the Department of Genetic Medicine, University of Geneva, Geneva, Switzerland. "We found that the vast majority of the protein coding genes we studied utilised often in a tissue-specific manner previously unknown set of exons [the regions of DNA within a gene that are transcribed to messenger RNA] outside the current boundaries of the annotated genes ", Professor Reymond will say.



EPO upholds limited patent on BRCA2 gene: singling out an ethnic group is a "dangerous precedent" says European Society of Human Genetics

Following the decision of the European Patent Office (EPO) to uphold the slimmed-down version of University of Utah Research Foundation's European patent on the BRCA2 breast cancer gene, Professor Gert Matthijs, from the Department of Human Genetics, Catholic University of Leuven, Belgium, and chair of the ESHG Patenting and Licensing Committee, said: "The patent owners have been able to rescue a small bit of their original patent on BRCA2 testing by putting Ashkenazi women into their claim. This apparently renders the test for the 6974delT mutation, which happens to be frequent in the Ashkenazi population, inventive, novel and industrially applicable. ..."

Geneticists oppose singling out Jewish women in European breast cancer patent

Jewish women in Europe may face genetic discrimination in access to breast cancer diagnosis if the patent on the BRCA2 gene, which is currently being disputed, is not withheld by the European Patent Office (EPO) on June 29. The European Society for Human Genetics (ESHG) is strongly opposed to the selection of a particular racial group as a diagnostic target in a gene patent claim and is calling on the EPO to take action to prevent this situation.

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European Human Genetics Conference 2022

June 11-14, 2022, Vienna, Austria

New retinal examination can predict a heart attack

Vienna, Austria: Combining information about the pattern of blood vessels in the retina with genetic data can enable accurate prediction of an individual’s risk of coronary artery disease (CAD) and its potentially fatal outcome, myocardial infarction (MI), commonly known as a heart attack. The discovery could lead to a simple screening process where an MI risk could be calculated when a person undergoes a routine eye test, researchers will tell the annual conference of the European Society of Human Genetics today (Monday).

“We already knew that variations in the vasculature of the retina might offer insights into our health. Given that retinal imaging is a non-invasive technique, we decided to investigate the health benefits we could obtain from these images. First, we studied the branching patterns of the retinal vasculature by calculating a measure named fractal dimension (Df) from data available from the UK Biobank (UKB). UKB includes demographical, epidemiological, clinical, imaging and genotyping data from over 500,000 participants across UK. We found that lower Df, simplified vessel branching patterns, is related to CAD and hence MI,” says Ms Ana Villaplana-Velasco, a PhD student at the Usher and Roslin Institutes, University of Edinburgh, Edinburgh, UK.

The researchers then developed a model that was able to predict MI risk prediction by studying UKB participants who had experienced an MI event after collection of their retinal images. The model included Df as well as traditional clinical factors, such as age, sex, systolic blood pressure, body mass index and smoking status to calculate personalised MI risk. “Strikingly, we discovered that our model was able to better classify participants with low or high MI risk in UKB when compared with established models that only include demographic data. The improvement of our model was even higher if we added a score related to the genetic propensity of developing MI”, Ms Villaplana-Velasco said.

“We wondered if the Df-MI association was influenced by shared biology, so we looked at the genetics of Df and found nine genetic regions driving retinal vascular branching patterns. Four of these regions are known to be involved in cardiovascular disease genetics. In particular, we found that these common genetic regions are involved in processes related to MI severity and recovery.”

These findings may also be useful in identifying propensity to other diseases. Variations in the retinal vascular pattern also reflect the development of other ocular and systemic diseases, such as diabetic retinopathy and stroke. The researchers believe it is possible that every condition may have a unique retinal variation profile. “We would like to investigate this further, as well as undertaking a sex-specific analysis. We know that females with a higher MI or CAD risk tend to have pronounced retinal vascular deviations when compared to the male population.  We would like to repeat our analysis separately in males and females to investigate if a sex-specific model for MI completes a better risk classification,” says Ms Villaplana-Velasco.

Even though the researchers knew that variations in retinal vasculature were associated with the state of health of an individual, their convincing results came as a surprise. “There have been multiple attempts to improve CAD and MI risk predictive models by accounting for retinal vascular traits, but these showed no significant improvement when compared with established models. In our case, we found that the clinical MI definition - the diagnostic codes that describe myocardial infarction events in medical records - is central to the successful development of predictive models, underpinning the need for developing robust disease definitions in large studies such as UKB. Once we validated our MI definition, we found that our model worked extremely well,” Ms Villaplana-Velasco said.

In the future, a simple retinal examination may be able to provide enough information to identify people at risk. The average age for an MI is 60, and the researchers found that their model achieved its best predictive performance more than five years before the MI event. ”So the calculation of an individualised MI risk from those over 50 years old would seem to be appropriate,” says Ms Villaplan-Velasco. ”This would enable doctors to suggest behaviours that could reduce risk, such as giving up smoking and maintaining normal cholesterol and blood pressure. Our work once more shows the importance of comprehensive analysis of data that is routinely collected and its value in the further development of personalised medicine.”

Professor Alexandre Reymond, chair of the conference, said: ”This study demonstrates  the importance of implementing prevention now,  and how personalised health is providing us with the tools to do so.”


Abstract C22.6: Decreased retinal vascular complexity is an early biomarker of myocardial infarction supported by a shared genetic control