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Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability
Authors:Benjamin Cogné  Sophie Ehresmann  Eliane Beauregard-Lacroix  Justine Rousseau  Thomas Besnard  Thomas Garcia  Slavé Petrovski  Shiri Avni  Kirsty McWalter  Patrick R. Blackburn  Stephan J. Sanders  Kévin Uguen  Jacqueline Harris  Julie S. Cohen  Moira Blyth  Anna Lehman  Jonathan Berg  Mindy H. Li  Philippe M. Campeau
Affiliation:1. Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France;2. INSERM, CNRS, UNIV Nantes, l’institut du thorax, 44007 Nantes, France;3. Centre Hospitalier Universitaire Sainte-Justine Research Centre, University of Montreal, Montreal, QC H3T 1C5, Canada;4. Department of Medicine, University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, VIC 3010, Australia;5. AstraZeneca Centre for Genomics Research, Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge CB2 0AA, UK;6. Visual Geometry Group, Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, UK;7. GeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA;8. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA;9. Center for Individualized Medicine, Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA;10. Department of Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA;11. UMR 1078, Génétique, Génomique Fonctionnelle et Biotechnologies, Inserm, L''Etablissement Français du Sang, Institut Brestois Santé Agro Matière, Université de Brest Occidentale, 29200 Brest, France;12. Service de Génétique médicale et de biologie de la reproduction, Centre Hospitalier Regional Universitaire Brest, 29200 Brest, France;13. Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD 21205, USA;14. Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205, USA;15. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;16. Department of Clinical Genetics, Chapel Allerton Hospital, Yorkshire Regional Genetics Service, Leeds Teaching Hospitals National Health Service Trust, Chapeltown Road, Leeds LS7 4SA, UK;17. Department of Pediatrics, University of British Columbia, Vancouver, BC V6H 3N1, Canada;18. Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK;19. Rush University Medical Center, Department of Pediatrics, Division of Genetics, Chicago, IL 60612, USA;20. Oxford Centre for Genomic Medicine, Oxford University Hospitals National Health Service Trust, Oxford OX3 7LE, UK;21. West of Scotland Regional Genetics Service, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK;22. Department of Medical Genetics, St. Olav’s Hospital, Trondheim University Hospital, 7006 Trondheim, Norway;23. Laboratory of Embryology and Genetics of Human Malformations, Institut National de la Santé et de la Recherche Médicale (Inserm), UMR 1163, Institut Imagine, 75015 Paris, France;24. Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France;25. Division of Genetics, Department of Pediatrics, University of Virginia Children’s Hospital, Charlottesville, VA 22903, USA;26. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;27. Texas Children’s Hospital, Houston, TX 77030, USA;28. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA;29. Baylor Genetics, Houston, TX 77021, USA;30. Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;31. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;32. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA;33. Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;34. Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden;35. Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden;36. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA;37. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, the Netherlands;38. Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands;39. Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA;40. Department of Pediatric Surgery, The McGovern Medical School at the University of Texas Health Science Center and Children’s Memorial Hermann Hospital, Houston, TX 77030, USA;41. Division of Genetics and Metabolism, Phoenix Children’s Hospital, Phoenix, AZ 85016, USA;42. Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA;43. Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland 4029, Australia;44. School of Medicine, The University of Queensland, Brisbane, Queensland 4029, Australia;45. Department of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway;46. Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA;47. Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolecent Medicine, Oslo University Hospital, Rikshospitalet, Pb 4950 Nydalen, N-0424 Oslo, Norway;48. Roberts Individualized Medical Genetics Center, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;49. Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA;50. Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA;51. Service de Génétique, Hôpital Necker—Enfants Malades, Assistance Publique—Hôpitaux de Paris (APHP), 75015 Paris, France;52. Service de Chirurgie Maxillofaciale et Plastique, Centre de référence des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, Assistance Publique—Hôpitaux de Paris (APHP), 75015 Paris, France;53. Division of Genetics, Birth Defects, and Metabolism, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA;54. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA;55. Service de Génétique, Centre Hospitalier Universitaire de Tours, 2 Boulevard Tonnellé, 37044 Tours, France;56. Inserm U1253, Ibrain, Université de Tours, 37032 Tours, France;57. Service de Génétique Clinique, Centre Référence Déficiences Intellectuelles de Causes Rares, Centre de Référence Anomalies du Développement, Centre Labellisé pour les Anomalies du Développement (CLAD) Ouest, Centre Hospitalier Universitaire de Rennes, 35203 Rennes, France;58. Institut de Génétique et Développement de Rennes, UMR 6290, Université de Rennes, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France;59. Centre Hospitalier Universitaire de Angers, Département de Biochimie et Génétique, 49933 Angers Cedex 9, France;60. Mitochondrial and Cardiovascular Pathophysiology (MITOVASC), Unité mixte de Recherche, Centre National de la Recherche Scientifique 6015, Inserm 1083, Université d’Angers, 49933 Angers, France;61. Centre Hospitalier Universitaire de Poitiers, Service de Génétique, BP577, 86021 Poitiers, France;62. Equipe d''accueil 3808, Université Poitiers, Poitiers 86034, France;63. Department of Medical Genetics, University of Alberta, Edmonton, AB T6G 2H7, Canada;64. Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA;65. Epilepsy Genetics Program, Department of Neurology, Boston Children’s Hospital, Boston, MA 02115, USA;66. Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;67. Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA;68. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK;69. Rosalind & Morris Goodman Cancer Research Center and Department of Medicine, McGill University, Montreal, QC H3A 1A3, Canada;70. Department of Biochemistry, McGill University and McGill University Health Center, Montreal, QC H3A 1A3, Canada;71. Department of Pharmacology, Creighton University Medical School, Omaha, NE 68178, USA;72. Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK;73. Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK;74. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK;75. Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA;76. Howard Hughes Medical Institute, Seattle, WA 98195, USA;77. Division of Pediatric Neurology, University of Alberta, Edmonton, AB, Canada;78. Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada;79. Department of Pediatrics, University of Montreal, Montreal, QC H3T1J4, Canada
Abstract:
Keywords:histone acetylation  intellectual disability  congenital malformations  autism spectrum disorder  neurodevelopmental disorders
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