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Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy
Affiliation:1. Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;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;4. Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile;5. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA;6. Institute of Human Genetics, University of Leipzig Medical Center, Leipzig 04103, Germany;7. Department of Pediatrics, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H4A 3J1, Quebec, Canada;8. Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica Scienze Materno-Infantili, Università degli studi di Genova, 16126 Genova, Italy;9. IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy;10. Division of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, ON, Canada;11. Department of Molecular Medicine and Surgery, Centre for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden;12. Department of Clinical Genetics, Karolinska University Hospital, Stockholm 17176, Sweden;13. Institute of Medical Genetics, University of Zurich, Schlieren-Zurich CH-8952, Switzerland;14. Neuroscience Center Zurich, University of Zurich and Eidgenössische Technische Hochschule, Zurich 8057, Switzerland;15. Genetics, Cook Children’s Physician Network, Fort Worth, TX 76104, USA;16. Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, Meyer Children’s Hospital, University of Florence, 50139 Florence, Italy;17. Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA;18. Division of Genetics, Rady Children’s Hospital of San Diego, San Diego, CA 92123, USA;19. Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen 72076, Germany;20. Laboratoire de Génétique Moléculaire et Génomique, Centre Hospitalier Universitaire de Rennes, Rennes 35033, France;21. Department of Genetics, Centre de Référence Déficiences Intellectuelles de Causes Rares, Pitié-Salpêtrière Hospital, Assistance Publique—Hôpitaux de Paris, Paris 75013, France;22. Groupe de Recherche Clinique Déficience Intellectuelle et Autisme, Sorbonne University, Paris 75006, France;23. West Midlands Regional Clinical Genetics Service, Birmingham Women’s and Children’s Hospital, National Health Service Foundation Trust, Birmingham B15 2TG, UK;24. Birmingham Health Partners, Birmingham Women’s and Children’s Hospital, National Health Service Foundation Trust, Birmingham B15 2TG, UK;25. Department of Neurology, Children’s Mercy Hospital and Clinics, Kansas City, MO 64108, USA;26. Medical Genetics, University of Siena, 53100 Siena, Italy;27. Genetica Medica, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy;28. Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK;29. Service de Génétique Clinique, Centre de Référence Maladies Rares Centre Labellisé Anomalies du Développement-Ouest, Centre Hospitalier Universitaire de Rennes, 35033 Rennes, France;30. Centre de Génétique Chromosomique, Groupement des Hôpitaux de l''Institut Catholique de Lille Hôpital Saint Vincent de Paul, 59020 Lille, France;31. Faculté de médecine de l’Université Catholoique de Lille, 59800 Lille, France;32. Department of Clinical Genetics, Aarhus University Hospital, 8200 Aarhus, Denmark;33. St. Vincent’s Children’s Hospital, Indianapolis, IN 46260, USA;34. Medical Genetic Unit, Italian Hospital of Lugano, Lugano, Switzerland; Università della Svizzera Italiana, 6900 Lugano, Switzerland;35. Oxford National Institute for Health Research Biomedical Research Centre, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK;36. Division of Neurology and Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;37. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104 USA;38. Department of Neuropediatrics, University Medical Center, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany;39. GeneDx, Gaithersburg, MD 20877, USA;40. Service de Génétique Médicale, Hôpital Hôtel-Dieu, Centre Hospitalier Universitaire de Nantes, 44093 Nantes, France;41. Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, FL 32610, USA;42. Mendelics Genomic Analysis, Sao Paulo 04013, Brazil;43. Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands;44. Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK;45. Department of Clinical Genetics, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands;46. Department of Clinical Genetics, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands;47. Division of Medical Genetics and Genomics, Spectrum Health, Grand Rapids, MI 49544, USA;48. Department of Neurology and Neurosurgery, Universidade de Federal de São Paulo, São Paulo 04023, Brazil;49. Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada;50. Neuropediatric Unit, Pediatric Department of Southern Switzerland, San Giovanni Hospital, 6500 Bellinzona, Switzerland;51. Rare Disease Initiative Zürich, Clinical Research Priority Program for Rare Diseases, University of Zurich, CH-8006 Zurich, Switzerland;52. Department of Pediatrics, Division of Genetics and Metabolism, University of South Florida, Tampa, FL 33606, USA;53. Section of Pediatric Neurology, Rady Children’s Hospital, San Diego, CA 92123, USA;54. Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA;55. Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA;56. Center for Pediatric Genomic Medicine, Children’s Mercy Hospital and Clinics, Kansas City, MO 64108, USA;57. School of Medicine, University of Missouri, Kansas City, MO 64108, USA;58. Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany;59. EA7364 Rares du Developpement Embryonnaire et du Metabolisme, Institut de Genetique Medicale, Centre Hospitalier Universitaire de Lille, University of Lille, F-59000 Lille, France;60. Division of Child Neurology and Inherited Metabolic Diseases, Department of General Paediatrics, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany;61. Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital and Clinics, Kansas City, MO 64108, USA;62. Pediatric Neurology and Neurophysiology, Instituto de Neurologia de Goiania, Goiania 74210, Brazil;63. Department of Medical Genetics, Assistance Publique – Hôpitaux de Marseille, Hôpital d’Enfants de La Timone, 13005 Marseille, France;64. Marseille Medical Genetics Center, Aix Marseille Univ, Inserm, U1251, Marseille, France;65. Center for Fetal Diagnostics, Aarhus University Hospital, 8200 Aarhus, Denmark;66. Department for Neurosurgery, University of Tübingen, 72076 Tübingen, Germany;67. Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, Toronto, M5G 1X8, ON, Canada;68. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA;69. Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester University National Health Service Foundation Trust, Health Innovation Manchester, Manchester M13 9WL, UK;70. Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Abstract:
Keywords:KMT2E  global developmental delay  intellectual disability  epilepsy  epileptic encephalopathy  autism  neurodevelopmental disorder  H3K4 methylation
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