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Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects,skeletal abnormalities,and immune dysregulation
Authors:Alban Ziegler  Rémi Duclaux-Loras  Céline Revenu  Fabienne Charbit-Henrion  Bernadette Begue  Karine Duroure  Linda Grimaud  Anne Laure Guihot  Valérie Desquiret-Dumas  Mohammed Zarhrate  Nicolas Cagnard  Emmanuel Mas  Anne Breton  Thomas Edouard  Clarisse Billon  Michael Frank  Estelle Colin  Guy Lenaers  Marianna Parlato
Affiliation:1. Department of Biochemistry and Molecular Biology, CHU d’Angers, 49000 Angers, France;2. University of Angers, MitoVasc, UMR CNRS 6015, INSERM 1083, 49933 Angers, France;3. Université de Paris, Imagine Institute, Laboratory of Intestinal Immunity, INSERM, UMR1163, 75015 Paris, France;4. Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France;5. Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, 75005 Paris, France;6. Department of Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, 75015 Paris, France;7. Department of Molecular Genetics, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, 75015 Paris, France;8. Genomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 et INSERM US24/CNRS UMS3633, Paris Descartes Sorbonne Paris Cité University, 75015 Paris, France;9. Bioinformatics Core Facility, INSERM-UMR 1163, Imagine Institute, 75015 Paris, France;10. IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse 31300, France;11. Centre de Référence des Maladies Rares Digestives, and Pediatric Clinical Research Unit, Toulouse Clinical Investigation Center INSERM U1436, Hôpital des Enfants, CHU de Toulouse, Toulouse 31300, France;12. Reference Centre for Marfan Syndrome and Reference Centre on Rare Bone Diseases, Pediatric Clinical Research Unit, Children’s Hospital, Toulouse University Hospital, RESTORE, INSERM UMR1301, 31300 Toulouse, France;13. Centre de Génétique, Centre de Référence des Maladies Vasculaires Rares, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France;14. Université de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France;15. Fédération de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France;16. Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d’Enfants, CHU Dijon, 21000 Dijon, France;17. Département de Génétique Médicale, CHU de Hautepierre, 67200 Strasbourg, France;18. Nephrology and Transplantation Department, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France;19. Medical Genetics Institute, Meir Medical Center, Kfar-Saba 4428164, Israel;20. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;21. Genomic Research Department, Emedgene Technologies, 67443 Tel Aviv, Israel;22. Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Parkville 3052, Melbourne, VIC, Australia;23. Department of Paediatrics, The University of Melbourne, 3010 Parkville, Melbourne, VIC, Australia;24. Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;25. Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India;26. Broad Center for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA;27. Department of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, WC1N 3BG London, UK;28. Department of Otolaryngology–Head & Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany;29. Institute of Human Genetics, Julius Maximilians University Würzburg, 97074 Würzburg, Germany;30. Molecular and Clinical Sciences Institute, St. George’s, University of London, Cranmer Terrace London, SW17 ORE London, UK;31. Innovative Medical Research Center, Mashhad Branch, Islamic Azdad University, Mashhad 9133736351, Iran;32. Department of Dermatology, CHU d’Angers, 49000 Angers, France
Abstract:
Keywords:connective tissue disorder  TGF-β signaling  Loeys-Dietz syndrome  joint hyperlaxity  arterial dilatation
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