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SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females
Authors:Francesca Clementina Radio  Kaifang Pang  Andrea Ciolfi  Michael A. Levy  Andrés Hernández-García  Lucia Pedace  Francesca Pantaleoni  Zhandong Liu  Elke de Boer  Adam Jackson  Alessandro Bruselles  Haley McConkey  Emilia Stellacci  Stefania Lo Cicero  Marialetizia Motta  Rosalba Carrozzo  Maria Lisa Dentici  Kirsty McWalter  Marco Tartaglia
Affiliation:1. Genetics and Rare Disease Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy;2. Division of Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA;3. Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON N6A5W9, Canada;4. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;5. Oncohaematology Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy;6. Department of Human Genetics, Radboudumc, 6525 GA Nijmegen, the Netherlands;7. Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 GA Nijmegen, the Netherlands;8. Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9 WL Manchester, UK;9. Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester University NHS Foundation Trust, M13 9WL Manchester, UK;10. Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy;11. GeneDx, Gaithersburg, MD 20877, USA;12. Inserm UMR 1231 GAD (Génétique des Anomalies du Développement), Université de Bourgogne, 21070 Dijon, France;13. UF Innovation en Diagnostic Génomique des Maladies Rares, CHU, Dijon Bourgogne, 21079 Dijon, France;14. Division of Medical Genetics, Department of Pediatrics, Cedars Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USA;15. Phoenix Children’s Hospital, Phoenix, AZ 85016, USA;16. Division of Medical Genetics, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA;17. McMaster Children’s Hospital, Hamilton, ON L8N 3Z5, Canada;18. Clinical genetics, NYU Langone Long Island School of Medicine, Mineola, NY 11501, USA;19. Center for Pediatric Genomic Medicine, Children’s Mercy Hospital, Kansas City, MO 64108, USA;20. Children’s Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada;21. Mendelics Genomic Analysis, Campo Belo - São Paulo 04013-000, Brazil;22. Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA;23. Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA;24. Ospedale Papa Giovanni XXIII, 24127 Bergamo, Italy;25. Azienda Socio Sanitaria Territoriale Lariana, 22100 Como, Italy;26. Dipartimento di Pediatria, Università di Padova, 35137 Padua, Italy;27. Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, VIC 3052, Australia;28. Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Melbourne, VIC 3052, Australia;29. Medical and Populations Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;30. Royal Devon & Exeter NHS Foundation Trust, Exeter EX2 5DW, UK;31. Department of Genetics, Hospices Civils de Lyon, Groupement Hospitalier Est, Claude Bernard Lyon 1 University, 69002 Lyon, France;32. Institute of Medical Genetics, University of Zurich, 8952 Schlieren, Zurich, Switzerland;33. Pediatric Neurology Unit, Ruth Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel;34. Genetics Institute, Rambam Health Care Campus, Rappaport Faculty of Medicine, Israel Institute of Technology, Haifa 3109601, Israel;35. Department of Genetics, CHEO, University of Ottawa, Ottawa, ON K1N 6N5, Canada;36. Connecticut Children’s Medical Center, University of Connecticut School of Medicine, Farmington, CT 06032, USA;37. Department of Clinical Genetics, Maastricht University Medical Center+, 6229 HX Maastricht, the Netherlands;38. Department of Medical Genetics, Shodair Children’s Hospital, Helena, MT 59601, USA;39. Ambry Genetics, Aliso Viejo, CA 92656, USA;40. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA;41. Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;42. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;43. Illumina Clinical Services Laboratory, San Diego, CA 92122, USA;44. Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” 34137 Trieste, Italy;45. Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA 98195, USA;46. Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden;47. CA de Génétique Clinique & Oncogénétique, CHU Amiens-Picardie, 80054 Amiens, France;48. Department of Clinical Genetics, Erasmus MC University Medical Center, 3015 GD Rotterdam, the Netherlands;49. Department of Developmental Biology, Oncode Institute, Erasmus MC, University Medical Center, 3015 GD Rotterdam, the Netherlands;50. Department of Pediatrics, Division of Medical Genetics, Levine Children’s Hospital Atrium Health, Charlotte, NC 28203, USA;51. Department of Medicine, Surgery & Health Science, University of Trieste, 34143 Trieste, Italy;52. Centre de Référence Maladies Rares « Anomalies du Développement et Syndromes Malformatifs », Centre de Génétique, FHU-TRANSLAD et Institut GIMI, 77908 Dijon, France;53. UMR 1231 GAD, Inserm - Université Bourgogne-Franche Comté, 77908 Dijon, France;54. Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA;55. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA;56. UOSD Genetica Medica del Grande Ospedale Metropolitano “Bianchi Melacrino Morelli” di Reggio Calabria, 89124 Reggio Calabria, Italy;57. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
Abstract:
Keywords:neurodevelopmental disorder  1p36  distal 1p36 deletion syndrome  proximal 1p36 deletion syndrome  obesity  DNA methylome analysis  episignature  X chromosome  genotype-phenotype correlations
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