Further delineation of BCAP31-linked intellectual disability: description of 17 new families with LoF and missense variants
| Autor: | Glen D. Thomson, Olga Calabrese, Hong Cui, Sandra Chantot Bastaraud, Frances Elmslie, Renee Carroll, Agnès Guët, Sandra Whalen, Anne Slavotinek, Thierry Billette de Villemeur, Vishal Kumar, Brian Kirmse, Patrick Yap, Elise Brischoux-Boucher, Florence Riccardi, Jenny Morton, Carroll Jennifer, Jonathan Levy, Manoelle Kossorotoff, Alessandro Mauro Spinelli, Elisabeth Forsythe, Annelies Dheedene, Anne McCabe, Cecile Cieuta Walti, Jozef Gecz, Anne Claude Tabet, Laurent Villard, Cyril Mignot, Kristen V. Truxal, Jessica N. Hartley, Annick Raas-Rothschild, Jillian R Ozmore, Marie Shaw, Jan Liebelt, Delphine Héron, Patrick Frosk, Benjamin Kamien, Jane A. Hurst, Antonella Pini |
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| Přispěvatelé: | UF de Génétique Clinique et Centre de Reference Anomalies du Développement et Syndromes Malformatifs, Sorbonne Université (SU), University of Adelaide, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Sherbrooke (UdeS), Women’s and Children’s Hospital [Adelaide], St George’s University Hospitals, Genetic Health Service New Zealand, Great Ormond Street Hospital for Children NHS Foundation Trust, Partenaires INRAE, University of Mississippi Medical Center (UMMC), Dartmouth Hitchcock Medical Center, University of Modena and Reggio Emilia, Hôpital Robert Debré, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Necker, King-Edward Memorial Hospital, Perth, Australia., Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Chaim Sheba Medical Center, IRCCS Istituto delle Scienze Neurologiche di Bologna [Bologna, Italy], Ospedale Bellaria [Bologna, Italy], University of Manitoba [Winnipeg], University of California, Ohio State University [Columbus] (OSU), Ghent University Hospital, GeneDx [Gaithersburg, MD, USA], Starship Children's Hospital, University of Auckland [Auckland], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), NHMRC grants APP1155224 and APP1091593 and Channel 7 Children’s Research Foundation, National Human Genome Research Institute of the National Institutes of Health under Award Number U01HG009599, Gall, Valérie, University of California (UC), ANS - Cellular & Molecular Mechanisms, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Care4Rare Canada Consortium [SDV]Life Sciences [q-bio] [SDV.GEN] Life Sciences [q-bio]/Genetics Deafness Loss of Function Mutation Intellectual disability Genetics research 2.1 Biological and endogenous factors Medicine Missense mutation Aetiology Child Genetics (clinical) Genetics & Heredity Dystonia Genetics 0303 health sciences [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology Liver Disease 030305 genetics & heredity Neurodevelopmental disorders Syndrome Phenotype Pedigree 3. Good health [SDV] Life Sciences [q-bio] Child Preschool Medical genetics Female medicine.symptom Adult medicine.medical_specialty Adolescent Clinical Sciences Mutation Missense Asymptomatic Article 03 medical and health sciences Rare Diseases Clinical Research Intellectual Disability Humans Preschool Loss function [SDV.GEN]Life Sciences [q-bio]/Genetics business.industry Neurosciences Membrane Proteins medicine.disease Brain Disorders Xq28 Hereditary Central Nervous System Demyelinating Diseases Mutation Missense Digestive Diseases business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | European Journal of Human Genetics European Journal of Human Genetics, Nature Publishing Group, 2021, ⟨10.1038/s41431-021-00821-0⟩ European Journal of Human Genetics, 2021, ⟨10.1038/s41431-021-00821-0⟩ Eur J Hum Genet European journal of human genetics : EJHG, vol 29, iss 9 European journal of human genetics, 29(9), 1405-1417. Nature Publishing Group |
| ISSN: | 1018-4813 1476-5438 |
| Popis: | International audience; The BCAP31 gene, located at Xq28, encodes BAP31, which plays a role in ER-to-Golgi anterograde transport. To date, BCAP31 pathogenic variants have been reported in 12 male cases from seven families (six loss of function (LoF) and one missense). Patients had severe intellectual disability (ID), dystonia, deafness, and central hypomyelination, delineating a so-called deafness, dystonia and cerebral hypomyelination syndrome (DDCH). Female carriers are mostly asymptomatic but may present with deafness. BCAP31 is flanked by the SLC6A8 and ABCD1 genes. Contiguous deletions of BCAP31 and ABCD1 and/or SLC6A8 have been described in 12 patients. Patients with deletions including BCAP31 and SLC6A8 have the same phenotype as BCAP31 patients. Patients with deletions of BCAP31 and ABCD1 have contiguous ABCD1 and DXS1375E/BCAP31 deletion syndrome (CADDS), and demonstrate a more severe neurological phenotype with cholestatic liver disease and early death. We report 17 novel families, 14 with intragenic BCAP31 variants (LoF and missense) and three with a deletion of BCAP31 and adjacent genes (comprising two CADDS patients, one male and one symptomatic female). Our study confirms the phenotype reported in males with intragenic LoF variants and shows that males with missense variants exhibit a milder phenotype. Most patients with a LoF pathogenic BCAP31 variant have permanent or transient liver enzyme elevation. We further demonstrate that carrier females (n = 10) may have a phenotype comprising LD, ID, and/or deafness. The male with CADDS had a severe neurological phenotype, but no cholestatic liver disease, and the symptomatic female had moderate ID and cholestatic liver disease. |
| Databáze: | OpenAIRE |
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