Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum DisordersClaire S Leblond1,2,3, Jutta Heinrich4, Richard Delorme1,2,5, Christian Proepper4, Catalina Betancur6,7,8, Guillaume Huguet1,2,3, Marina Konyukh1,2,3, Pauline Chaste1,2,3, Elodie Ey1,2,3, Maria Rastam9, Henrik Anckarsäter10, Gudrun Nygren11, I. Carina Gillberg11, Jonas Melke12, Roberto Toro1,2,3, Beatrice Regnault13, Fabien Fauchereau1,2,3, Oriane Mercati1,2,3, Nathalie Lemière1,2,3, David Skuse14, Martin Poot15, Richard Holt16, Anthony P Monaco16, Irma Järvelä17, Katri Kantojärvi17, Raija Vanhala17, Sarah Curran18, David A Collier19, Patrick Bolton18,19, Andreas Chiocchetti20, Sabine M. Klauck20, Fritz Poustka21, Christine M. Freitag21, Regina Waltes21, Marnie Kopp21, Eftichia Duketis21, Elena Bacchelli22, Fiorella Minopoli22, Liliana Ruta23, Agatino Battaglia24, Luigi Mazzone25, Elena Maestrini22, Ana F. Sequeira26,27,28, Barbara Oliveira26,27,28, Astrid Vicente26,27,28, Guiomar Oliveira29, Dalila Pinto30, Stephen W Scherer30, Diana Zelenika31, Marc Delepine31, Mark Lathrop31, Dominique Bonneau32,33, Vincent Guinchat34, Françoise Devillard35, Brigitte Assouline34, Marie-Christine Mouren5, Marion Leboyer36,37,38, Christopher Gillberg11,39, Tobias M Boeckers4 and Thomas Bourgeron1,2,3*(1) Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France
(2) CNRS URA 2182 ‘Genes, synapses and cognition’, Institut Pasteur, Paris, France
(3) University Paris Diderot, Paris, France
(4) Institute of Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany
(5) Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Department of Child and Adolescent Psychiatry, Paris, France
(6) Inserm, U952, Paris, France
(7) CNRS, UMR 7224, Paris, France
(8) UPMC Univ Paris 06, Paris, France
(9) Department of Clinical Sciences in Lund, Lund University, Lund, Sweden
(10) Institute of Clinical Sciences, Lund University, Malmö, Sweden
(11) Gillberg Neuropsychiatry Centre. University of Gothenburg, Göteborg, Sweden
(12) Institute of Neuroscience and Physiology, Department of Pharmacology, Gothenburg University, Sweden
(13) Eukaryote Genotyping Platform. Genopole. Institut Pasteur, Paris, France
(14) Behavioural and Brain Sciences Unit, Institute of Child Health, University College London, UK
(15) Department of Medical Genetics, University Medical Center Utrecht, Utrecht, NL
(16) Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
(17) Department of Medical Genetics, University of Helsinki, Helsinki, Finland
(18) Academic Department of Child & Adolescent Psychiatry, Institute of Psychiatry, King’s College London, UK
(19) Social Genetic Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, UK
(20) Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
(21) Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe University, Frankfurt am Main, Germany
(22) Department of Biology, University of Bologna, Italy
(23) Division of Child Neurology and Psychiatry, Department of Paediatrics, University of Catania, Catania, Italy
(24) Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, Calambrone (Pisa), Italy
(25) Division of Child Neurology and Psychiatry, Department of Pediatrics, University of Catania, Catania, Italy
(26) Instituto Nacional de Saude Dr Ricardo Jorge, Lisbon, Portugal
(27) Instituto Gulbenkian de Ciencia, Oeiras, Portugal
(28) Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, Lisboa, Portugal
(29) Unidade Neurodesenvolvimento e Autismo, Centro Investigação e Formação Clinica, Hospital Pediátrico Coimbra e Faculdade Medicina, Universidade Coimbra, Portugal
(30) The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Canada
(31) Centre National de Génotypage, Evry, France
(32) Inserm U771 and CNRS 6214, Angers, F-49000, France
(33) Département de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, F-49000 France
(34) CADIPA - Centre de Ressources Autisme Rhône-Alpes, Saint Egrève, France
(35) Genetics Department, Hôpital Couple-Enfant, Grenoble, France
(36) INSERM, U955, Psychiatrie Génétique, Créteil, 94000, France
(37) Université Paris Est, Faculté de Médecine, Créteil, France
(38) AP-HP, Hôpital H. Mondor - A. Chenevier, Département de Psychiatrie, Créteil, 94000, France
(39) Institute of Child Health, University College London, London, UK