Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function.

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Title: Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function.
Authors: Asadollahi R; Institute of Medical Genetics, University of Zurich, Zurich, Switzerland. R.Asadollahi@greenwich.ac.uk.; Faculty of Engineering and Science, University of Greenwich London, Medway Campus, Chatham Maritime, London, UK. R.Asadollahi@greenwich.ac.uk., Ahmad A; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Boonsawat P; Institute of Medical Genetics, University of Zurich, Zurich, Switzerland., Shahanoor Hinzen J; Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA., Lohse M; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Bouazza-Arostegui B; Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Sun S; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Utesch T; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Sommer JD; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Ilic D; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Padmanarayana M; Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA., Fischermanns K; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Ranjan M; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Boll M; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Ka C; Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.; Service de Génétique Médicale et Biologie de la Reproduction, CHU de Brest, Brest, France., Piton A; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France., Mattioli F; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France., Isidor B; Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France., Õunap K; Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.; Institute of Clinical Medicine, University of Tartu, Tartu, Estonia., Reinson K; Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.; Institute of Clinical Medicine, University of Tartu, Tartu, Estonia., Wojcik MH; Divisions of Newborn Medicine and Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Marshall CR; Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada., Mercimek-Andrews S; Department of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada., Matsumoto N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Miyake N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.; Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan., Stephan BO; Clinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Honjo RS; Clinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Bertola DR; Clinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Kim CA; Clinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Yusupov R; Division of Clinical Genetics, Joe DiMaggio Children's Hospital, Hollywood, FL, USA., Mefford HC; Center for Pediatric Neurological Disease Research, St. Jude Children's Hospital, Memphis, TN, USA., Christodoulou J; Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia., Lee J; Department of Metabolic Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Heath O; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Brown NJ; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Baker N; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Stark Z; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Delatycki M; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Lake NJ; Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Genetics, Yale School of Medicine, New Haven, CT, USA., Zeidler S; Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands., Zuurbier L; Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam, The Netherlands., Maas SM; Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam, The Netherlands., de Kruiff CC; Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands., Rajabi F; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Section of Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Rodan LH; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA., Coury SA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.; Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA., Platzer K; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany., Oppermann H; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany., Abou Jamra R; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany., Beblo S; Center for Pediatric Research, University Hospital for Children and Adolescents, and Centre for Rare Diseases, University Hospital Leipzig, Leipzig, Germany., Maxton C; Zentrum für Kinderneurologie, Hamburg, Germany., Śmigiel R; Department of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases, Medical University of Wrocław, Wrocław, Poland., Underhill H; Department of Pediatrics, Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA., Dubbs H; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Rosen A; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Helbig KL; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA., Helbig I; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA.; The Center for Epilepsy and Neurodevelopmental Disorders, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ruggiero SM; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA., Fitzgerald MP; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Kraemer D; Institute of Medical Genetics, University of Zurich, Zurich, Switzerland., Prada CE; Division of Genetics and Rare Diseases, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Tenney J; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.; Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Jayakar P; Division of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL, USA., Redon S; Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.; Service de Génétique Médicale et Biologie de la Reproduction, CHU de Brest, Brest, France., Lefranc J; Pediatrics Department, Competence Center for Epilepsy, Hôpital Morvan, CHU Brest, Brest, France., Uguen K; Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.; Service de Génétique Médicale et Biologie de la Reproduction, CHU de Brest, Brest, France., Race S; Division of Biochemical Genetics, BC Children's Hospital, Vancouver, British Columbia, Canada., Efthymiou S; Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK., Maroofian R; Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK., Houlden H; Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK., Coppens S; Center of Human Genetics, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium., Deconinck N; 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., Ashokkumar B; School of Biotechnology, Madurai Kamaraj University, Madurai, India., Varalakshmi P; School of Biotechnology, Madurai Kamaraj University, Madurai, India., Gowda K VR; Indira Gandhi Institute of Child Health, Bangalore, India.; Bangalore Child Neurology and Rehabilitation Center, Bangalore, India., Eghbal F; Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran., Ghayoor Karimiani E; Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran., Heidari M; Myelin Disorders Clinic, Department of Pediatric Neurology, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran., Neidhardt J; Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.; Research Center Neurosensory Science, Carl von Ossietzky University Oldenburg, Oldenburg, Germany., Owczarek-Lipska M; Human Genetics, Medical Faculty, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.; Research Center Neurosensory Science, Carl von Ossietzky University Oldenburg, Oldenburg, Germany., Korenke GC; Department of Neuropediatrics, University Children's Hospital, Klinikum Oldenburg, Oldenburg, Germany., Bamshad MJ; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA., Campeau PM; Department of Pediatrics, CHU Sainte-Justine and University of Montreal, Montreal, Quebec, Canada., Lehman A; Department of Medical Genetics, The University of British Columbia, Vancouver, British Columbia, Canada., Hendon LG; Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA., Wentzensen IM; GeneDx, LLC, Gaithersburg, MD, USA., Monaghan KG; GeneDx, LLC, Gaithersburg, MD, USA., Chen Y; GeneDx, LLC, Gaithersburg, MD, USA., Szuto A; The Hospital for Sick Children, Toronto, Ontario, Canada., Cohn RD; The Hospital for Sick Children, Toronto, Ontario, Canada., Au PYB; Department of Medical Genetics, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Hübner C; Department of Neuropediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Boschann F; Institut für Medizinische Genetik und Humangenetik, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Biomedical Innovation Academy, Clinician Scientist Program, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany., Manickam K; Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA., Koboldt DC; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Rad A; Arcensus GmbH, Rostock, Germany., Oprea G; Arcensus GmbH, Rostock, Germany., Bachman KK; Department of Pediatrics, Women's and Children's Institute, Geisinger Medical Center, Danville, PA, USA., Seeley AH; Department of Pediatrics, Women's and Children's Institute, Geisinger Medical Center, Danville, PA, USA., Agolini E; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Terracciano A; Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Carmelo P; Medical and Laboratory Genetics Unit, A.O.R.N. 'Antonio Cardarelli', Naples, Italy., Bupp C; Corewell Health West Helen DeVos Children's Hospital, Grand Rapids, MI, USA., Grysko B; Corewell Health West Helen DeVos Children's Hospital, Grand Rapids, MI, USA., Rein-Rothschild A; The Institute for Rare Diseases, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.; School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel., Ben Zeev B; School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.; Pediatric Neurology Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel., Margolin A; Division of Medical Genetics, Arnold Palmer Hospital Orlando Health, Orlando, FL, USA., Morrison J; Division of Medical Genetics, Arnold Palmer Hospital Orlando Health, Orlando, FL, USA., Dagli A; Division of Medical Genetics, Arnold Palmer Hospital Orlando Health, Orlando, FL, USA., Stolerman E; Greenwood Genetic Center, Greenwood, SC, USA., Louie RJ; Greenwood Genetic Center, Greenwood, SC, USA., Washington C; Greenwood Genetic Center, Greenwood, SC, USA., Stevens SJC; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Heijligers M; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands., Alkuraya FS; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Lisfeld J; Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Neu A; Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Paoli Monteiro F; Medical Department, Mendelics Genomic Analysis, São Paulo, Brazil., Santos Pessoa AL; Federal University of Ceará - UFC and Hospital Infantil Albert Sabin, Fortaleza, Brazil., Camelo-Filho AE; Federal University of Ceará - UFC and Hospital Infantil Albert Sabin, Fortaleza, Brazil., Kok F; 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Département de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France., Charles P; Département de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France., Nava C; Département de génétique, Hôpital Pitié-Salpêtrière, Centre de Références Déficiences Intellectuelles de Causes Rares, AP-HP.Sorbonne Université, Paris, France., Bernhard FP; Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany., Kühn AA; Movement Disorders and Neuromodulation Unit, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Thoms S; Biochemistry and Molecular Medicine, Medical School OWL, Bielefeld University, Bielefeld, Germany., Morrie RD; Trace Neuroscience, South San Francisco, CA, USA., Mekhoubad S; Trace Neuroscience, South San Francisco, CA, USA., Green EM; Trace Neuroscience, South San Francisco, CA, USA., Barmada SJ; University of Michigan School of Medicine, Ann Arbor, MI, USA., Gitler AD; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Jahn O; Neuroproteomics Group, Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.; Translational Neuroproteomics Group, Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany., Rhee JS; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Rosenmund C; Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Mitkovski M; City Campus Light Microscopy Facility, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Sticht H; Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Sun H; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany., Le Gac G; Univ Brest, Inserm, EFS, UMR 1078, GGB, Brest, France.; Service de Génétique Médicale et Biologie de la Reproduction, CHU de Brest, Brest, France., Taschenberger H; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Brose N; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany., Dittman JS; Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA., Rauch A; Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.; Children's Hospital, University Zurich, Zurich, Switzerland., Lipstein N; Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. Lipstein@FMP-berlin.de.; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany. Lipstein@FMP-berlin.de.
Source: Nature genetics [Nat Genet] 2025 Nov; Vol. 57 (11), pp. 2691-2704. Date of Electronic Publication: 2025 Oct 22.
Publication Type: Journal Article
Journal Info: Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:1546-1718
DOI:10.1038/s41588-025-02361-5