• Institute of Medical Genetics, University of Zurich, Zurich, Switzerland

    Reza Asadollahi, Paranchai Boonsawat, Dennis Kraemer & Anita Rauch

  • Faculty of Engineering and Science, University of Greenwich London, Medway Campus, Chatham Maritime, London, UK

    Reza Asadollahi

  • Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany

    Aisha Ahmad, Mareike Lohse, Mrinalini Ranjan, Jeong Seop Rhee, Holger Taschenberger, Nils Brose & Noa Lipstein

  • Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany

    Aisha Ahmad, Mareike Lohse, Siqi Sun, Tillmann Utesch, Jonas D. Sommer, Dragana Ilic, Kati Fischermanns, Moritz Boll, Han Sun & Noa Lipstein

  • Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA

    Jasmine Shahanoor Hinzen, Murugesh Padmanarayana & Jeremy S. Dittman

  • Institute of Neurophysiology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Boris Bouazza-Arostegui & Christian Rosenmund

  • Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France

    Chandran Ka, Sylvia Redon, Kevin Uguen & Gerald Le Gac

  • Service de Génétique Médicale et Biologie de la Reproduction, CHU de Brest, Brest, France

    Chandran Ka, Sylvia Redon, Kevin Uguen & Gerald Le Gac

  • Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France

    Amélie Piton & Francesca Mattioli

  • Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France

    Bertrand Isidor

  • Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia

    Katrin Õunap & Karit Reinson

  • Institute of Clinical Medicine, University of Tartu, Tartu, Estonia

    Katrin Õunap & Karit Reinson

  • Divisions of Newborn Medicine and Genetics and Genomics, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Monica H. Wojcik

  • Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Monica H. Wojcik

  • Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Monica H. Wojcik

  • Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

    Christian R. Marshall

  • Department of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada

    Saadet Mercimek-Andrews

  • Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Naomichi Matsumoto & Noriko Miyake

  • Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan

    Noriko Miyake

  • Clinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    Bruno de Oliveira Stephan, Rachel Sayuri Honjo, Debora R. Bertola & Chong Ae Kim

  • Division of Clinical Genetics, Joe DiMaggio Children’s Hospital, Hollywood, FL, USA

    Roman Yusupov

  • Center for Pediatric Neurological Disease Research, St. Jude Children’s Hospital, Memphis, TN, USA

    Heather C. Mefford

  • Brain and Mitochondrial Research Group, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

    John Christodoulou & Nicole J. Lake

  • Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia

    John Christodoulou, Natasha J. Brown & Zornitza Stark

  • Department of Metabolic Medicine, The Royal Children’s Hospital, Melbourne, Victoria, Australia

    Joy Lee

  • Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

    Joy Lee, Oliver Heath, Natasha J. Brown, Naomi Baker, Zornitza Stark & Martin Delatycki

  • Department of Genetics, Yale School of Medicine, New Haven, CT, USA

    Nicole J. Lake

  • Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands

    Shimriet Zeidler

  • Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam, The Netherlands

    Linda Zuurbier & Saskia M. Maas

  • Emma Children’s Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands

    Chris C. de Kruiff

  • Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, USA

    Farrah Rajabi, Lance H. Rodan & Stephanie A. Coury

  • Department of Pediatrics, Section of Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Farrah Rajabi

  • Division of Genetics, Brigham and Women’s Hospital, Boston, MA, USA

    Stephanie A. Coury

  • Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

    Konrad Platzer, Henry Oppermann & Rami Abou Jamra

  • Center for Pediatric Research, University Hospital for Children and Adolescents, and Centre for Rare Diseases, University Hospital Leipzig, Leipzig, Germany

    Skadi Beblo

  • Zentrum für Kinderneurologie, Hamburg, Germany

    Caroline Maxton

  • Department of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases, Medical University of Wrocław, Wrocław, Poland

    Robert Śmigiel

  • Department of Pediatrics, Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA

    Hunter Underhill

  • Division of Neurology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Holly Dubbs, Alyssa Rosen, Katherine L. Helbig, Ingo Helbig, Sarah McKeown Ruggiero & Mark P. Fitzgerald

  • Epilepsy NeuroGenetics Initiative (ENGIN), Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Katherine L. Helbig, Ingo Helbig, Sarah McKeown Ruggiero & Mark P. Fitzgerald

  • The Center for Epilepsy and Neurodevelopmental Disorders, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Ingo Helbig

  • Department of Biomedical and Health Informatics (DBHi), Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Ingo Helbig

  • Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ingo Helbig & Mark P. Fitzgerald

  • Division of Genetics and Rare Diseases, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Carlos E. Prada

  • Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Carlos E. Prada

  • Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Jeffrey Tenney

  • Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Jeffrey Tenney

  • Division of Genetics and Metabolism, Nicklaus Children’s Hospital, Miami, FL, USA

    Parul Jayakar

  • Pediatrics Department, Competence Center for Epilepsy, Hôpital Morvan, CHU Brest, Brest, France

    Jérémie Lefranc

  • Division of Biochemical Genetics, BC Children’s Hospital, Vancouver, British Columbia, Canada

    Simone Race

  • Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK

    Stephanie Efthymiou, Reza Maroofian & Henry Houlden

  • Center of Human Genetics, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium

    Sandra Coppens

  • Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des Enfants Reine Fabiola, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium

    Nicolas Deconinck

  • School of Biotechnology, Madurai Kamaraj University, Madurai, India

    Balasubramaniem Ashokkumar & Perumal Varalakshmi

  • Indira Gandhi Institute of Child Health, Bangalore, India

    Vykunta Raju Gowda K

  • Bangalore Child Neurology and Rehabilitation Center, Bangalore, India

    Vykunta Raju Gowda K

  • Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran

    Fatemeh Eghbal & Ehsan Ghayoor Karimiani

  • Myelin Disorders Clinic, Department of Pediatric Neurology, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Morteza Heidari

  • Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany

    John Neidhardt & Marta Owczarek-Lipska

  • Research Center Neurosensory Science, Carl von Ossietzky University Oldenburg, Oldenburg, Germany

    John Neidhardt & Marta Owczarek-Lipska

  • Department of Neuropediatrics, University Children’s Hospital, Klinikum Oldenburg, Oldenburg, Germany

    G. Christoph Korenke

  • Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA

    Michael J. Bamshad

  • Department of Pediatrics, CHU Sainte-Justine and University of Montreal, Montreal, Quebec, Canada

    Philippe M. Campeau

  • Department of Medical Genetics, The University of British Columbia, Vancouver, British Columbia, Canada

    Anna Lehman

  • Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA

    Laura G. Hendon

  • GeneDx, LLC, Gaithersburg, MD, USA

    Ingrid M. Wentzensen, Kristin G. Monaghan & Yanmin Chen

  • The Hospital for Sick Children, Toronto, Ontario, Canada

    Anna Szuto & Ronald D. Cohn

  • Department of Medical Genetics, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

    Ping Yee Billie Au

  • Department of Neuropediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Christoph Hübner

  • Institut für Medizinische Genetik und Humangenetik, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Felix Boschann

  • BIH Biomedical Innovation Academy, Clinician Scientist Program, Berlin Institute of Health at Charité–Universitätsmedizin Berlin, Berlin, Germany

    Felix Boschann

  • Division of Genetic and Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

    Kandamurugu Manickam

  • Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA

    Kandamurugu Manickam & Daniel C. Koboldt

  • The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

    Daniel C. Koboldt

  • Arcensus GmbH, Rostock, Germany

    Aboulfazl Rad & Gabriela Oprea

  • Department of Pediatrics, Women’s and Children’s Institute, Geisinger Medical Center, Danville, PA, USA

    Kristine K. Bachman & Andrea H. Seeley

  • Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Emanuele Agolini & Alessandra Terracciano

  • Medical and Laboratory Genetics Unit, A.O.R.N. “Antonio Cardarelli”, Naples, Italy

    Piscopo Carmelo

  • Corewell Health West Helen DeVos Children’s Hospital, Grand Rapids, MI, USA

    Caleb Bupp & Bethany Grysko

  • The Institute for Rare Diseases, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel

    Annick Rein-Rothschild

  • School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel

    Annick Rein-Rothschild & Bruria Ben Zeev

  • Pediatric Neurology Unit, The Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel

    Bruria Ben Zeev

  • Division of Medical Genetics, Arnold Palmer Hospital Orlando Health, Orlando, FL, USA

    Amy Margolin, Jennifer Morrison & Aditi Dagli

  • Greenwood Genetic Center, Greenwood, SC, USA

    Elliot Stolerman, Raymond J. Louie & Camerun Washington

  • Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands

    Servi J. C. Stevens & Malou Heijligers

  • Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Fowzan S. Alkuraya

  • College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    Fowzan S. Alkuraya

  • Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Jasmin Lisfeld

  • Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Axel Neu

  • Medical Department, Mendelics Genomic Analysis, São Paulo, Brazil

    Fabíola Paoli Monteiro

  • Federal University of Ceará – UFC and Hospital Infantil Albert Sabin, Fortaleza, Brazil

    André Luiz Santos Pessoa & Antonio Edvan Camelo-Filho

  • Department of Neurology, Neurogenetics Center, University of São Paulo, São Paulo, Brazil

    Fernando Kok

  • Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA

    Dwight Koeberl & Kacie Riley

  • Département de Génétique, Centre de référence des malformations et maladies congénitales du cervelet, Hôpital Trousseau, AP-HP.Sorbonne Université, Paris, France

    Lydie Burglen

  • Service de Neuropédiatrie-Pathologie du Développement, Centre de Référence Neurogénétique, Hôpital Trousseau, FHU I2-D2, AP-HP.Sorbonne Université, Paris, France

    Diane Doummar & Bénédicte Héron

  • Département de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France

    Cyril Mignot, Boris Keren, Perrine Charles & Caroline Nava

  • Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany

    Felix P. Bernhard

  • Movement Disorders and Neuromodulation Unit, Department of Neurology, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Andrea A. Kühn

  • Biochemistry and Molecular Medicine, Medical School OWL, Bielefeld University, Bielefeld, Germany

    Sven Thoms

  • Trace Neuroscience, South San Francisco, CA, USA

    Ryan D. Morrie, Shila Mekhoubad & Eric M. Green

  • University of Michigan School of Medicine, Ann Arbor, MI, USA

    Sami J. Barmada

  • Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA

    Aaron D. Gitler

  • Neuroproteomics Group, Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany

    Olaf Jahn

  • Translational Neuroproteomics Group, Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany

    Olaf Jahn

  • City Campus Light Microscopy Facility, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany

    Mišo Mitkovski

  • Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany

    Heinrich Sticht

  • Children’s Hospital, University Zurich, Zurich, Switzerland

    Anita Rauch

    • N.L., R.A., A. Rauch, H.T. and N. Brose conceptualized the study. N.L., R.A., A. Rauch, H.T., C.R., J.S.R., H. Sun, M.M., J.S.D., G.L.G. and H. Sticht devised the methodology. N.L., A.A., B.B.-A., H.T., R.A., M.L., M.M., M.P., D.I., P.B., T.U., M.B., M.R., J.S.D., G.L.G. and S.T. conducted the formal analysis. N.L., A.A., R.A., P.B., C.K., J.S.H., M.L., B.B.-A., S.S., T.U., J.D.S., D.I., O.J., M.B., M.P., K.F., D. Kraemer, J.D.S. and H. Sticht performed the investigation. N.L., N. Brose and R.A. wrote the original draft of the paper. N.L., R.A., P.B., M.L., M.M., T.U., H. Sticht, B.B.-A., C.K., G.L.G., J.S.D. and A.E.C.-F. were responsible for visualization. N.L., R.A., A. Rauch, N. Brose, C.R., J.S.D. and G.L.G. supervised the study. N.L., R.A., A. Rauch and N. Brose acquired funding. A.A.K., A. Rad, A.D., A.D.G., A.E.C.-F., A.H.S., A.L., A. Rosen, A.L.S.P., A.M., A.N., A.P., A.R.-R., A.S., A.T., B.A., B.B.Z., B.d.O.S., B.G., B.H., B.I., B.K., C.A.K., C. Maxton, C.B., C.C.d.K., C.E.P., C.H., C.N., C.R.M., C.W., C. Mignot, D.C.K., D.D., D.R.B., D. Koeberl, E.A., E.G.K., E.M.G., E.S., F.B., F.E., F.K., F.M., F.P.B., F.P.M., F.R., F.S.A., G.C.K., G.O., H.C.M., H.D., H.H., H.O., H.U., I.H., I.M.W., J. Lisfeld, J.C., J. Lefranc, J.M., J.N., J. Lee, J.T., K. Riley, K. Reinson, K.G.M., K.L.H., K.K.B., K.M., K.Õ., K.P., K.U., L.B., L.G.H., L.H.R., L.Z., M. Heijligers, M.D., M.H.W., M.J.B., M. Heidari, M.O.-L., M.P.F., N. Baker, N. Matsumoto, N.D., N.J.B., N.J.L., N. Miyake, O.H., P. Charles, P. Carmelo, P.J., P.M.C., P.V., P.Y.B.A., R.A.J., R.C., R.M., R.S.H., R.J.L., R.Ś., R.Y., R.D.M., S.A.C., S.C., S.B., S.E., S. Race, S.J.B., S.J.C.S., S.M., S.M.-A., S.M.M., S.M.R., S. Redon, S.Z., V.R.G.K., Y.C. and Z.S. acquired resources (genetic, diagnostic and clinical information). All authors read, reviewed, edited and approved the paper.