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Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease
Affiliation:1. Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;2. Texas Children’s Hospital, Houston, TX, USA;3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;4. School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China;5. Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;6. Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;7. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA;8. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA;9. Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel;10. Boys Town National Research Hospital, Boys Town, NE, USA;11. Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians University Munich, Munich, Germany;12. German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany;13. Department of Radiology, Baylor College of Medicine, Houston, TX, USA;14. E.B. Singleton Department of Pediatric Radiology, Texas Children’s Hospital, Houston, TX, USA;15. Autism & Developmental Medicine Institute, Geisinger, Danville, PA, USA;16. Department of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA;17. Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA;18. Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA;19. Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA;20. Division of Clinical Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA;21. Paediatric Radiology Department, AP-HP, Hôpital Necker Enfants Malades, Université Paris Cité, Institut Imagine INSERM U1163, 75015 Paris, France;22. Service de Médecine Génomique des Maladies Rares – APHP, Hôpital Necker Enfants Malades, Université de Paris, Paris, France;23. Genomic Medicine Center, Children’s Mercy Hospital, Kansas City, MO, USA;24. University of Missouri Kansas City School of Medicine, Kansas City, MO, USA;25. Department of Neurology, UT Health Science Center at Houston, McGovern Medical School, Houston, TX, USA;26. Neuroscience Department, Meyer Children’s Hospital IRCCS, Florence, Italy;27. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;28. Lifetime Neurodevelopmental Care, San Francisco, CA, USA;29. North East Thames Regional Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK;30. Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;31. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;32. Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;33. GeneDx, Gaithersburg, MD, USA;34. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l’Interrégion Est, Fédération Hospitalo-Universitaire Médecine TRANSLationnelle et Anomalies du Développement, Centre Hospitalier Universitaire Dijon, Equipe Genetics of Developmental Anomalies-INSERM UMR 1231, Dijon, France;35. Functional Unit for Diagnostic Innovation in Rare Diseases, FHU-TRANSLAD, Dijon Bourgogne University Hospital, Dijon, France;36. INSERM UMR1231 GAD “Génétique des Anomalies du Développement,” FHU-TRANSLAD, University of Burgundy, Dijon, France;37. Department of Genetics and Reference Center for Development Disorders and Intellectual Disabilities, Dijon Bourgogne University Hospital, Dijon, France;38. Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany;39. Institute of Mother and Child, Kasprzaka 17a, 02-211 Warsaw, Poland;40. Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road L103, Portland, OR, USA;41. Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait;42. University of Florence, Florence, Italy;43. Chair of Experimental Genetics, TUM School of Life Sciences, Technische Universität München, Alte Akademie 8, 85354 Freising, Germany;44. Technische Universität München, Freising-Weihenstephan, Germany;45. Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China;46. Kunming Institute of Zoology Chinese Academy of Sciences, the Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Hong Kong SAR, China;47. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;1. Department of Molecular Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan;2. Department of Neurology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan;3. Department of iPS Cell Applied Medicine, Graduate School of Medicine, Kansai Medical University, Osaka, Japan;4. Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan;5. Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan;6. Department of Neurology, Tohoku University Graduate School of Medicine, Miyagi, Japan;7. Department of Medical Genetics, Tohoku University Graduate School of Medicine, Miyagi, Japan;8. Department of Neuromuscular Research, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, National Centre Hospital, Tokyo, Japan;9. Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, Japan;10. Department of Neurology, Wakayama Medical University, Wakayama, Japan;11. Department of Neurology, Kansai Medical University, Osaka, Japan;12. Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan;13. Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan;1. Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA;2. MOE Key Laboratory of Metabolism and Molecular Medicine, Shanghai Medical College of Fudan University, Shanghai, China;3. Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China;4. Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China;5. Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA;6. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA;7. Disease Networks Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland;8. Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland;1. Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health, 85764 Neuherberg, Germany;2. Munich School of Data Science, Helmholtz Zentrum München – German Research Center for Environmental Health, 85764 Neuherberg, Germany;3. TUM School of Medicine, Technical University Munich and Klinikum Rechts der Isar, 81675 Munich, Germany;4. Technical University of Munich (TUM), School of Medicine, Graduate School of Experimental Medicine, 81675 Munich, Germany;5. MRC Integrative Epidemiology Unit, University of Bristol, BS8 2BN Bristol, UK;6. Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, M13 9PT Manchester, UK;1. Sorbonne Université, Paris Brain Institute (ICM), Pitié-Salpêtrière Hospital, AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, CS21414, 75646 PARIS Cedex 13, France;2. Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy;3. German Center for Neurodegenerative Disease (DZNE), 53127 Bonn, Germany;4. Department of Neurology, University Hospital of Bonn, 53111 Bonn, Germany;5. Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, 6525 Nijmegen, the Netherlands;6. Neurology Department, Hospital de Santo António, Centro Hospitalar Universitário de Santo António, 4099-001 Porto, Portugal;7. CGPP, IBMC-Institute for Molecular and Cell Biology & UnIGENe, i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal;8. German Center for Neurodegenerative Disease (DZNE), 72076 Tübingen, Germany;9. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research & Center of Neurology, University of Tübingen, 72076 Tübingen, Germany;10. Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesu’ Children’s Research Hospital, IRCCS, 00165 Rome, Italy;11. Department of Neuromuscular Diseases, UCL Queen’s Square Institute of Neurology, Queen’s Square House, Queen’s Square, WC1N 3BG London, UK;12. Department of Neuroscience and Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy;13. Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, 52428 Jülich, Germany;14. Institute of Clinical Neuroscience and Medical Psychology and Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany;15. Molecular Medicine & Neurogenetics, IRCCS Fondazione Stella Maris, 56128 Calambrone, Italy;16. University of Washington, Seattle, WA 98195, USA;17. Center for Rare Movement Disorders, Medical University of Innsbruck, 6020 Innsbruck, Austria;18. Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, 25121 Brescia, Italy;19. German Center for Neurodegenerative Disease (DZNE), München, Germany;20. Department of Neurology, Friedrich-Baur Institute, University Hospital of Ludwig-Maximilians-University, Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany;21. Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department, S. Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy;22. San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy;23. Scientific Institute I.R.C.C.S. Eugenio Medea, 23842 Bosisio Parini, Italy;24. Pediatric Neurology Department, Sant Joan de Déu Hospital, 08950 Barcelona, Spain;25. Department of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin, 10117 Berlin, Germany;26. Department of Neurology, Leiden University Medical Center, 2333 Leiden, the Netherlands;27. Department of Clinical Genetics, Dijon University Hospital, 21000 Dijon, France;28. Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, 45147 Essen, Germany;29. Department of Neurology, Clermont-Ferrand University Hospital, 63000 Clermont-Ferrand, France;30. Gardner Family Center for Parkinson’s Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH 45219, USA;31. Sapienza University of Rome, Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, 04100 Latina, Italy;32. Computational Biomedicine, Institute for Advanced Simulations IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52428 Jülich, Germany;33. Department of Biotechnology, Università degli Studi di Verona, 37134 Verona, Italy;34. Neurology Department, Tel-Aviv Sourasky Medical Center, 6329302 Tel-Aviv, Israel;35. Sackler School of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel;36. Pediatric Movement Disorders Clinic, Pediatric Neurology Unit, Wolfson Medical Center, 5822012 Holon, Israel;37. University Bordeaux, Equipe « Neurogénétique Translationnelle - NRGEN », INCIA CNRS UMR5287 Université Bordeaux and Centre de Reference Maladies Rares « Neurogénétique », Service de Génétique Médicale, Bordeaux University Hospital (CHU Bordeaux), 33000 Bordeaux, France;38. MMDN, University Montpellier, EPHE, INSERM and Expert Center for Neurogenetic Diseases, CHU, 34095 Montpellier, France;39. Department of Neurology, Strasbourg University Hospital, 67098 Strasbourg, France;40. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964; CNRS-UMR7104; University of Strasbourg, 67400 Illkirch-Graffenstaden, France;41. Department of Neurovascular Molecular Genetics, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, 75010 Paris, France;1. Knight Diagnostic Laboratories, Oregon Health & Science University, Portland, OR 97239, USA;2. Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA;3. Information Technology Group, Oregon Health & Science University, Portland, OR 97201, USA;4. Integrated Genomics Laboratory, Oregon Health & Science University, Portland, OR 97239, USA;5. Knight Cancer Institute, Community Outreach and Engagement, Oregon Health & Science University, Portland, OR 97201, USA;6. University of Oregon, School of Journalism and Communication, Portland, OR 97209, USA;7. OHSU-PSU School of Public Health, Portland, OR 97239, USA;8. Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA;9. Division of Oncological Sciences, Oregon Health & Science University, Portland, OR 97239, USA;1. Department of Computer Science, University of California, Los Angeles, Los Angeles, CA 90095, USA;2. Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA;3. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA;4. Dana-Farber Cancer Institute, Boston, MA, USA;5. Brigham and Women’s Hospital, Boston, MA, USA;6. Harvard Medical School, Boston, MA, USA;7. Department of Neurology, UCLA, Los Angeles, CA, USA;8. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA;9. Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA;10. Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA
Abstract:
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  • Keywords:DHX9  DExD/H-box RNA helicases  neurodevelopmental disorders  Charcot-Marie-Tooth disease  R-loops  DNA damage repair  homologous recombination  epilepsy  neuropathy  allelic series
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