ESHG Policy Statements
We present, on behalf of EuroGentest and the European Society of Human Genetics, guidelines for the evaluation and validation of next-generation sequencing (NGS) applications for the diagnosis of genetic disorders. The work was performed by a group of laboratory geneticists and bioinformaticians, and discussed with clinical geneticists, industry and patients’ representatives, and other stakeholders in the field of human genetics. The statements that were written during the elaboration of the guidelines are presented here. The background document and full guidelines are available as supplementary material. They include many examples to assist the laboratories in the implementation of NGS and accreditation of this service. The work and ideas presented by others in guidelines that have emerged elsewhere in the course of the past few years were also considered and are acknowledged in the full text. Interestingly, a few new insights that have not been cited before have emerged during the preparation of the guidelines. The most important new feature is the presentation of a ‘rating system’ for NGS-based diagnostic tests. The guidelines and statements have been applauded by the genetic diagnostic community, and thus seem to be valuable for the harmonization and quality assurance of NGS diagnostics in Europe.
The Letter to the editor in reaction to Wolf SM, Annas GJ, Elias S. Patient Autonomy and Incidental Findings in Clinical Genomics. Science 340,1049-1050 (2013).
ESHG calls for prudent use of WGS-based testing
Van El CG1 & Dondorp WJ4, De Wert GMWR3,4, Cornel MC1,2,3 (on behalf of the ESHG Public and Professional Policy Committee)
(1) Section Community Genetics, Department of Clinical Genetics and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands
(2) Center for Medical Systems Biology, Leiden, the Netherlands
(3) Centre for Society and the Life Sciences, Nijmegen, the Netherlands
(4) Department of Health, Ethics and Society; Research Schools CAPHRI & GROW, Maastricht University, Maastricht, the Netherlands
In their Policy Forum contribution Patient autonomy and incidental findings in clinical genomics Susan Wolf et al. criticize the American College of Medical Genetics (ACMG) for giving up on well-established principles of patient autonomy and informed consent. The European Society of Human Genetics (ESHG) recently also called for more prudence. The ACMG presents WGS-based diagnostic testing as an opportunity for screening. The ESHG position is that whenever possible, such testing should be targeted to genome regions linked to the indication. Wider testing requires a justification in terms of necessity and proportionality. Adding screening targets to a diagnostic test violates the necessity criterion. Imposing this extra testing upon patients who need an answer to their clinical problem is at odds with respect for autonomy. As stated by Wolf et al., people have a right to decline testing on the basis of their own assessment of burdens and benefits. However, with regard to reporting unsolicited findings, the ESHG does acknowledge that the patient's ”˜right not to know' may sometimes have to give way to professional responsibilities with regard to the interests both of the patient himself (who may not have foreseen and considered a specific finding) and of his close relatives (”˜duty to warn'). Where testing of children is concerned, the child's best interest may override the parental ”˜right (not) to know'. Pending further debate, we urge a more cautious attitude specifically including the patients' and physicians' perspectives.
 S.M. Wolf, G.J. Annas, S. Elias. Patient Autonomy and Incidental Findings in Clinical Genomics. Science 340,1049 (2013).
 C.G. van El et al. Eur J Hum Genet., 21, 580 (2013).
 W. Dondorp, B. Sikkema-Raddatz, C. de Die-Smulders, G. de Wert, Hum Mutat., 33,916 (2012).
In a letter published in the journal Science on 30 August, Professor Martina Cornel, chair of the Professional and Public Policy Committee of ESHG and colleagues call for restraint in the use of diagnostic testing based on whole-genome sequencing. Wherever possible, such testing should be restricted to those genome regions linked to the patient's indications, they say, and wider testing needs to be justified in terms of necessity. Adding additional targets to a diagnostic test would be a violation of this, they say.
However, in the case of unsolicited findings, the patient's right not to know may sometimes have to be secondary to clinical geneticists' professional responsibilities, say the authors. The patient may not have foreseen a specific finding and in some cases the physician will have a moral duty to warn close relatives. Pending further debate, a cautious approach continues to be warranted, they say.
Letter in Science (for subscribers only)
The letter by Carla van El et al summarises the Recommendations of the ESHG concerning on Whole Genome Sequencing in Health Care (Recommendations and Background Document) published in the European Journal of Human Genetics