C06 Clinical Genetics II
Chair: K. Kjaer

C31 Screening and maternal transmission instability of intermediate-size and premutation FMR1 alleles in 24,446 mother-newborn pairs from the general population
F. Rousseau^1,2, S. Lévesque¹, C. Dombrowski¹, M. Morel¹, R. Réhel¹, J. S. Côté¹, J. Bussières¹, K. Morgan³;
¹URGHM, Centre de recherche du Centre hospitalier universitaire de Québec, Quebec, PQ, Canada, ²CanGeneTest consortium & Université Laval, Québec, PQ, Canada, ³McGill University Hospital Centre, Montreal General Hospital Research Center, Montréal, PQ, Canada.

C32 Familial inherited microtia caused by a benign CNV amplification at chromosome 4pter
I. G. Balikova¹, K. Martens¹, C. Melotte¹, S. Van Vooren², Y. Moreau³, H. Starke⁴, D. Vetrie⁵, H. Fiegler⁵, N. Carter⁶, T. Liehr⁴, G. Matthijs¹, J. Fryns¹, I. Casteels⁷, K. Devriendt¹, J. R. Vermeesch¹;
¹Center for Human Genetics, Leuven, Belgium, ²ESAT-SISTA KU - Leuven, Leuven, Belgium, ³ESAT-SISTA, KU-Leuven, Leuven, Belgium, ⁴Institute of Human Genetics and Anthropology, Jena, Germany, ⁵Wellcome Trust Sanger Institute, Hinxton, United Kingdom, ⁶Wellcome Trust Sanger Institute,, Hinxton, United Kingdom, ⁷Department of Ophthalmology, KU - Leuven, Leuven, Belgium.

C33 Gene dosage, craniofacial and neurological development and Williams-Beuren syndrome.
M. Tassabehji¹, P. Hammond², S. Gribble³, W. Beckett¹, A. Karmiloff-Smith⁴, M. Peippo⁵, L. Brueton⁶, P. Lunt⁷, K. Metcalfe⁸, D. Donnai⁹, N. Carter¹⁰;
¹University of Manchester, Manchester, United Kingdom, ²UCL, London, United Kingdom, ³The Wellcome Trust Sanger Institute, Cambridge, United Kingdom, ⁴Birkbeck College, University of London, United Kingdom, ⁵Helsinki University Central Hospital, Helsinki, Finland, ⁶Birmingham Women's Hospital, Birmingham, United Kingdom, ⁷Bristol Royal Hospital for Sick Children, Bristol, United Kingdom, ⁸St Mary's Hospital, Manchester, United Kingdom, ⁹University of Manchester and St Mary's Hospital, Manchester, United Kingdom, ¹⁰The Wellcome Trust Sanger Institute, Canbridge, United Kingdom.

C34 Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients.
N. Sabherwal¹, F. Bangs², R. Röth¹, B. Weiss¹, K. Jantz¹, E. Tiecke², G. K. Hinkel³, C. Spaich⁴, B. P. Hauffa⁵, H. van der Kamp⁶, J. Kapeller¹, C. Tickle², G. Rappold¹;
¹Department of Molecular Human Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany, ²Division of Cell and Developmental Biology, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dundee, United Kingdom, ³Gemeinschaftspraxis, Dresden, Germany, ⁴Institute of Clinical Genetics, Klinikum Stuttgart, Stuttgart, Germany, ⁵Zentrum für Kinderheilkunde, Universitätsklinikum Essen, Essen, Germany, ⁶Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands.

C35 Chromosomal imbalances detected in patients with cerebral cortex malformations and epilepsy through array−CGH technique
F. Novara¹, T. Pramparo¹, R. Guerrini², B. Dalla Bernardina³, O. Zuffardi¹;
¹Biologia Generale e Genetica Medica, Pavia, Italy, ²Unità di Neurologia Infantile, Ospedale Pediatrico A Meyer - Università di Firenze, Firenze, Italy, ³Servizio Neuropsichiatria Infantile, Policlinico GB Rossi, Università di Verona, Verona, Italy.

C36 Activating SOS1 mutations cause Noonan syndrome
M. Tartaglia¹, L. Pennacchio^2,3, C. Zhao⁴, K. K. Yadav⁴, V. Fodale¹, A. Sarkozy^5,6, B. Pandit⁷, K. Oishi⁷, S. Martinelli¹, W. Schackwitz^2,3, A. Ustaszewska^2,3, J. Martin^2,3, J. Bristow^2,3, C. Carta¹, F. Lepri^5,6, C. Neri^5,6, I. Vasta⁸, K. Gibson⁹, C. J. Curry¹⁰, J. P. Lopez Siguero¹¹, M. C. Digilio¹², G. Zampino⁸, B. Dallapiccola^5,6, D. Bar-Sagi⁴, B. D. Gelb⁷;
¹Istituto Superiore di Sanità, Rome, Italy, ²Lawrence Berkeley National Laboratory, Berkeley, CA, United States, ³Joint Genome Institute, Walnut Creek, CA, United States, ⁴New York University School of Medicine, New York, NY, United States, ⁵IRCCS-CSS, San Giovanni Rotondo, Italy, ⁶Istituto CSS-Mendel, Rome, Italy, ⁷Mount Sinai School of Medicine, New York, NY, United States, ⁸Università Cattolica, Rome, Italy, ⁹Royal Children’s Hospital, Herston, Australia, ¹⁰Genetic Medicine Central California, Fresno, CA, United States, ¹¹Hospital Materno-Infantil, Malaga, Spain, ¹²Ospedale "Bambino Gesù", Rome, Italy.

C07 Molecular and biochemical basis of disease II
Chair: J. Beckman

C37 Mutations in the SPG11 gene, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum
G. Stevanin^1,2, F. M. Santorelli³, H. Azzedine¹, P. Coutinho⁴, P. Denora^1,3, E. Martin¹, A. Lossos⁵, B. Fontaine⁶, A. Filla⁷, E. Bertini³, A. Durr^1,2, A. Brice^1,2;
¹INSERM UMR679 - NEB, Paris, France, ²APHP- Pitie-Salpetriere Hosptital, Dpt Genetics Cytogenetics, Paris, France, ³IRCCS-Bambino Gesù Children’s Hospital, Rome, Italy, ⁴Hospital S. Sebastiao and UnIGENe, Porto, Portugal, ⁵Hadassah-Hebrew University Medical Center, Jerusalem, Israel, ⁶INSERM U546, Paris, France, ⁷Federico II University, Naples, Italy.

C38 OST3 mutation in non-syndromic mental retardation: expanding the spectrum of congenital disorders of glycosylation?
F. Molinari¹, S. Romano¹, W. Morelle², P. de Lonlay¹, A. Munnich¹, L. Colleaux¹;
¹INSERM U781, Paris, France, ²UMR CNRS/USTL 8570, Lille, France.

C39 A defect in the ionotropic glutamate receptor 6 gene (GLUR6) causes autosomal recessive mental retardation
M. M. Motazacker¹, B. Rost², T. Hucho¹, M. Garshasbi¹, K. Kahrizi³, R. Ullmann¹, F. Behjati³, R. Vazifehmand³, A. Tzschach¹, L. R. Jensen¹, D. Schmitz⁴, H. Najmabadi³, H. H. Ropers¹, A. W. Kuss¹;
¹Max-Planck-Institute for molecular genetics, Berlin, Germany, ²Neuroscience research center (NWFZ), Charité, Berlin, Germany, ³University of social welfare and rehabilitation sciences, Tehran, Iran (Islamic Republic of), ⁴Neuroscience research center (NWFZ), Charité, Berlin, Germany.

C40 Mutation of a potassium channel-related gene in progressive myoclonic epilepsy
R. Azizieh, P. Van Bogaert, J. Désir, A. Aeby, L. De Meirleir, J. Laes, F. Christiaens, M. J. Abramowicz;
IRIBHM, Brussels, Belgium.

C41 Mutations in TCF-4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction
J. Amiel¹, M. Rio¹, L. de Pontual¹, R. Redon², V. Malan¹, N. Boddaert³, P. Plouin⁴, N. Carter², S. Lyonnet¹, A. Munnich¹, L. Colleaux¹;
¹INSERM U-781, Université Paris-Descartes, Faculté de Médecine; AP-HP, Hôpital Necker-Enfants Malades, Paris, France, ²The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom, ³Pediatric Radiology and INSERM U-797, Paris, France, ⁴Clinical Neurophysiology Unit and INSERM U-663, Paris, France.

C42 Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)
A. Reis¹, C. Zweier¹, M. M. Peippo², J. Hoyer¹, S. Sousa³, A. Bottani⁴, J. Clayton-Smith⁵, W. Reardon⁶, J. Saraiva³, A. Cabral³, I. Göhring¹, K. Devriendt⁷, T. de Ravel⁷, E. K. Bijlsma⁸, R. C. M. Hennekam^9,10, A. Orrico¹¹, M. Cohen¹², A. Dreweke¹³, P. Nürnberg¹⁴, A. Rauch¹;
¹Inst. of Human Genetics, Univ. Erlangen-Nuremberg, Erlangen, Germany, ²The Family Federation of Finland, Helsinki, Finland, ³Pediatrics Hospital, Coimbra, Portugal, ⁴Division of Medical Genetics, Geneva, Switzerland, ⁵St Mary's Hospital, Manchester, United Kingdom, ⁶Our Lady's Hospital for Sick Children, Dublin, Ireland, ⁷Centre for Human Genetics, Leuven, Belgium, ⁸Centre for Human and Clinical Genetics, Leiden, The Netherlands, ⁹Institute of Child Health, London, United Kingdom, ¹⁰Dept. of Pediatrics, Amsterdam, The Netherlands, ¹¹Azienda Ospedaliera Universitaria Senese, Siena, Italy, ¹²Kinderzentrum München, Munich, Germany, ¹³Computer Science Dept. 2, Erlangen, Germany, ¹⁴Cologne Center for Genomics (CCG), Cologne, Germany.

C08 Analysis of complex diseases
Chair: T. Meitinger

C43 Powerful methods for whole genome association analysis of quantitative traits in samples of related individuals
Y. S. Aulchenko¹, N. Amin¹, N. Belonogova², D. de Koning³, C. Haley³, C. M. van Duijn¹;
¹Erasmus MC Rotterdam, Rotterdam, The Netherlands, ²Institute of Cytology & Genetics, Novosibirsk, Russian Federation, ³Roslin Institute, Edinburgh, United Kingdom.

C44 Optimizing information for linkage genomescreen in a large and inbred pedigree with a high density SNP map
C. Bellenguez^1,2, C. Ober³, C. Bourgain^2,1;
¹Univ Paris-Sud, UMR-S535, Villejuif F-94817, France, ²INSERM, Villejuif F-94817, France, ³Department of Human Genetics, The University of Chicago, Chicago, IL, United States.

C45 Epistasis for physiological variables in admixed populations
M. Fenger¹, A. Linneberg², O. Pedersen³, T. Hansen⁴, T. Jøregensen²;
¹University of Copenhagen, Hvidovre, Denmark, ²Research Centre for Prevention and Health, Glostrup, Denmark, ³Steno Diabetes Center, Gentofte, Denmark, ⁴Steno Diabetes Centre, Gentofte, Denmark.

C46 A powerful approach to detect parent-of-origin effects in whole-genome association scans of quantitative traits
N. M. Belonogova^1,2, Y. S. Aulchenko^1,3;
¹Institute of Cytology & Genetics SD RAS, Novosibirsk, Russian Federation, ²Department of Cytology & Genetics, Novosibirsk State University, Novosibirsk, Russian Federation, ³Department of Epidemiology & Biostatistics, Erasmus MC, 3000 CA Rotterdam, The Netherlands.

C47 Quantifying the increase in human individual genome-wide heterozygosity through isolate break-up and admixture
I. Rudan¹, Z. Biloglav², A. Vorko-Jovic², I. Kolcic², O. Polasek², L. Zgaga², T. Zemunik³, R. Mulic³, D. Ropac³, D. Stojanovic⁴, D. Puntaric⁵, R. Stevanovic⁶, H. Campbell¹;
¹Faculty of Medicine, Edinburgh, United Kingdom, ²Faculty of Medicine, Zagreb, Croatia, ³Faculty of Medicine, Split, Croatia, ⁴Faculty of Medicine, Rijeka, Croatia, ⁵Faculty of Medicine, Osijek, Croatia, ⁶Institute for Public Health, Zagreb, Croatia.

C48 CHROMSCAN: Genome-wide association mapping
A. R. Collins;
University of Southampton, Southampton, United Kingdom.

C09 Cancer genetics
Chair: R. Seruca

C49 Screening for splice defects: application to BRCA1 and BRCA2 unknown variants (UV)
V. Caux-Moncoutier¹, S. Pagès-Berhouet¹, D. Michaux¹, A. De Pauw¹, M. Gauthier-Villars¹, D. Stoppa-Lyonnet^1,2, C. Houdayer^1,3;
¹Institut Curie, Paris, France, ²INSERM U509, Paris, France, ³UMR INSERM 745, Paris, France.

C50 HNPCC-associated missense mutations in MSH2 may lead to failure of the protein to bind mismatched DNA
S. E. Ollila¹, D. Dermadi¹, J. Jiricny², M. Nyström¹;
¹Department of Biological and Environmental Sciences, Division of Genetics, University of Helsinki, Helsinki, Finland, ²Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland.

C51 MUTYH-associated polyposis (MAP): spectrum and frequency of extracolonic lesions
D. Christian, V. Steinke, S. Uhlhaas, P. Propping, W. Friedl, S. Aretz;
Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.

C52 A genome-wide SNP screen for bowel cancer susceptibility alleles
I. Tomlinson¹, R. Houlston², CORGI consortium, NSCCG;
¹London Research Institute, London, United Kingdom, ²Institute of Cancer Research, Sutton, United Kingdom.

C53 Hereditary Diffuse Gastric Cancer (HDGC) patients and CDH1 mutations: a systematic review of the literature
C. Oliveira¹, R. Karam¹, C. Graziadio², H. Pinheiro¹, S. Sousa¹, R. Seruca^1,3;
¹Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal, ²Department of Genetics, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (FFFCMPA), Porto Alegre, Brasil, Porto Alegre, Brazil, ³Medical Faculty of the University of Porto, Porto, Portugal, Porto, Portugal.

C54 The identification of (ETV6/)RUNX1-regulated genes in lymphopoiesis using histone deacetylase inhibitors in ETV6/RUNX1-positive lymphoid leukaemic cells
J. Starkova¹, J. Madzo¹, G. Cario², T. Kalina¹, A. Ford³, M. Zaliova¹, O. Hrusak¹, J. Trka¹;
¹CLIP – Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, Charles University, 2nd Medical School, Prague, Czech Republic, ²Department of Paediatrics, University Hospital Schleswig-Holstein, Kiel, Germany, ³Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.

C10 Therapy for genetic disease
Chair: V. van Heyningen

C55 Analysis of the genomic insertion sites of viral gene therapy vectors using next generation sequencing technologies.
C. Bauser¹, M. Schmidt², C. von Kalle²;
¹GATC Biotech, Konstanz, Germany, ²National Center for Tumor Diseases (NCT), Heidelberg, Germany.

C56 Correction of VLCAD deficiency and prediction of mutation severity with bezafibrate: how to kill two birds with one stone.
S. Gobin-Limballe¹, F. Djouadi¹, F. Aubey¹, S. Olpin², S. Yamaguchi³, R. Wanders⁴, T. Fukao⁵, J. Kim⁶, J. Bastin¹;
¹CNRS UPR 9078, Paris, France, ²Sheffield Children's Hospital, Sheffield, United Kingdom, ³Shimane School of medicine, Shimane, Japan, ⁴Academic Medical Center, Amsterdam, The Netherlands, ⁵Gifu University, Gifu, Japan, ⁶Medical College of Wisconsin, Milwaukee, WI, United States.

C57 Allele specific silencing of the disease-causing gene in South African patients with SCA7 using RNAi
J. Scholefield¹, M. Weinberg², P. Arbuthnot², M. Wood³, J. Greenberg⁴;
¹Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa, ²Department of Molecular Medicine and Haematology, Wits, Johannesburg, South Africa, ³Department of Physiology, Anatomy and Genetics, Oxford, Oxford, United Kingdom, ⁴Institute of Infectious Disease and Molecular Medicine, UCT, Cape Town, South Africa.

C58 Nonsense-mediated mRNA decay regulates response of cystic fibrosis patients to gentamicin
L. Linde¹, S. Boelz^2,3, M. Nissim-Rafinia¹, Y. S. Oren¹, M. Wilschanski⁴, Y. Yaakov⁴, G. Neu-Yilik^2,3, A. E. Kulozik^2,3, E. Kerem⁴, B. Kerem¹;
¹Department of Genetics, Life Sciences Institute, The Hebrew University, Jerusalem, Israel, ²Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany, ³Department for Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany, ⁴CF Center, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.

C59 Harmless selection of genetically manipulated human stem keratinocytes
T. Magnaldo, V. Bergoglio, E. Warrick, F. Larcher, O. Chevallier-Lagente, M. Del Rio;
CNRS, Villejuif, France.

C60 Development of liver disease despite mannose treatment in two patients with CDG-Ib
K. Mention, F. Lacaille, V. Valayannopoulos, S. Romano, F. Jaubert, Y. De Keyser, N. Seta, P. De Lonlay;
Necker Enfants Malades, PARIS, France.