Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

Affiliations

• ¹ Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA. Electronic address: [email protected].
• ² Broad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
• ³ Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK; Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile.
• ⁴ Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
• ⁵ Institute of Human Genetics, University of Leipzig Medical Center, Leipzig 04103, Germany.
• ⁶ Department of Pediatrics, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H4A 3J1, Quebec, Canada; Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica Scienze Materno-Infantili, Università degli studi di Genova, 16126 Genova, Italy; IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
• ⁷ Division of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, ON, Canada.
• ⁸ Department of Molecular Medicine and Surgery, Centre for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm 17176, Sweden.
• ⁹ Institute of Medical Genetics, University of Zurich, Schlieren-Zurich CH-8952, Switzerland; Neuroscience Center Zurich, University of Zurich and Eidgenössische Technische Hochschule, Zurich 8057, Switzerland.
• ¹⁰ Genetics, Cook Children's Physician Network, Fort Worth, TX 76104, USA.
• ¹¹ Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, University of Florence, 50139 Florence, Italy.
• ¹² Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA; Division of Genetics, Rady Children's Hospital of San Diego, San Diego, CA 92123, USA.
• ¹³ Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen 72076, Germany.
• ¹⁴ Laboratoire de Génétique Moléculaire et Génomique, Centre Hospitalier Universitaire de Rennes, Rennes 35033, France.
• ¹⁵ Division of Genetics, Rady Children's Hospital of San Diego, San Diego, CA 92123, USA.
• ¹⁶ Department of Genetics, Centre de Référence Déficiences Intellectuelles de Causes Rares, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris 75013, France; Groupe de Recherche Clinique Déficience Intellectuelle et Autisme, Sorbonne University, Paris 75006, France.
• ¹⁷ West Midlands Regional Clinical Genetics Service, Birmingham Women's and Children's Hospital, National Health Service Foundation Trust, Birmingham B15 2TG, UK; Birmingham Health Partners, Birmingham Women's and Children's Hospital, National Health Service Foundation Trust, Birmingham B15 2TG, UK.
• ¹⁸ Department of Neurology, Children's Mercy Hospital and Clinics, Kansas City, MO 64108, USA.
• ¹⁹ Medical Genetics, University of Siena, 53100 Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy.
• ²⁰ Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
• ²¹ Service de Génétique Clinique, Centre de Référence Maladies Rares Centre Labellisé Anomalies du Développement-Ouest, Centre Hospitalier Universitaire de Rennes, 35033 Rennes, France.
• ²² Centre de Génétique Chromosomique, Groupement des Hôpitaux de l'Institut Catholique de Lille Hôpital Saint Vincent de Paul, 59020 Lille, France; Faculté de médecine de l'Université Catholoique de Lille, 59800 Lille, France.
• ²³ Department of Clinical Genetics, Aarhus University Hospital, 8200 Aarhus, Denmark.
• ²⁴ St. Vincent's Children's Hospital, Indianapolis, IN 46260, USA.
• ²⁵ Medical Genetic Unit, Italian Hospital of Lugano, Lugano, Switzerland; Università della Svizzera Italiana, 6900 Lugano, Switzerland.
• ²⁶ Oxford National Institute for Health Research Biomedical Research Centre, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
• ²⁷ Division of Neurology and Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
• ²⁸ Division of Neurology and Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104 USA; Department of Neuropediatrics, University Medical Center, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
• ²⁹ GeneDx, Gaithersburg, MD 20877, USA.
• ³⁰ Service de Génétique Médicale, Hôpital Hôtel-Dieu, Centre Hospitalier Universitaire de Nantes, 44093 Nantes, France.
• ³¹ Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, FL 32610, USA.
• ³² Mendelics Genomic Analysis, Sao Paulo 04013, Brazil.
• ³³ Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.
• ³⁴ Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.
• ³⁵ Department of Clinical Genetics, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
• ³⁶ Department of Clinical Genetics, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands.
• ³⁷ Division of Medical Genetics and Genomics, Spectrum Health, Grand Rapids, MI 49544, USA.
• ³⁸ Department of Neurology and Neurosurgery, Universidade de Federal de São Paulo, São Paulo 04023, Brazil.
• ³⁹ Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
• ⁴⁰ Department of Neuropediatrics, University Medical Center, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
• ⁴¹ Neuropediatric Unit, Pediatric Department of Southern Switzerland, San Giovanni Hospital, 6500 Bellinzona, Switzerland.
• ⁴² Institute of Medical Genetics, University of Zurich, Schlieren-Zurich CH-8952, Switzerland; Neuroscience Center Zurich, University of Zurich and Eidgenössische Technische Hochschule, Zurich 8057, Switzerland; Rare Disease Initiative Zürich, Clinical Research Priority Program for Rare Diseases, University of Zurich, CH-8006 Zurich, Switzerland.
• ⁴³ Department of Pediatrics, Division of Genetics and Metabolism, University of South Florida, Tampa, FL 33606, USA.
• ⁴⁴ Section of Pediatric Neurology, Rady Children's Hospital, San Diego, CA 92123, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
• ⁴⁵ Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, Kansas City, MO 64108, USA; School of Medicine, University of Missouri, Kansas City, MO 64108, USA.
• ⁴⁶ Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
• ⁴⁷ EA7364 Rares du Developpement Embryonnaire et du Metabolisme, Institut de Genetique Medicale, Centre Hospitalier Universitaire de Lille, University of Lille, F-59000 Lille, France.
• ⁴⁸ Department of Pediatrics, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H4A 3J1, Quebec, Canada.
• ⁴⁹ Division of Child Neurology and Inherited Metabolic Diseases, Department of General Paediatrics, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
• ⁵⁰ School of Medicine, University of Missouri, Kansas City, MO 64108, USA; Department of Pathology and Laboratory Medicine, Children's Mercy Hospital and Clinics, Kansas City, MO 64108, USA.
• ⁵¹ Pediatric Neurology and Neurophysiology, Instituto de Neurologia de Goiania, Goiania 74210, Brazil.
• ⁵² Department of Medical Genetics, Assistance Publique - Hôpitaux de Marseille, Hôpital d'Enfants de La Timone, 13005 Marseille, France; Marseille Medical Genetics Center, Aix Marseille Univ, Inserm, U1251, Marseille, France.
• ⁵³ Department of Clinical Genetics, Aarhus University Hospital, 8200 Aarhus, Denmark; Center for Fetal Diagnostics, Aarhus University Hospital, 8200 Aarhus, Denmark.
• ⁵⁴ Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany; Department for Neurosurgery, University of Tübingen, 72076 Tübingen, Germany.
• ⁵⁵ Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, Toronto, M5G 1X8, ON, Canada.
• ⁵⁶ Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
• ⁵⁷ Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University National Health Service Foundation Trust, Health Innovation Manchester, Manchester M13 9WL, UK.
• ⁵⁸ Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].