De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features
| Autor: | Bertrand Isidor, Rami Abou Jamra, Virginie Carmignac, Yannis Duffourd, Helio Pedro, Eriko Koshimizu, Maja Hempel, Tobias Bartolomaeus, Martin Chevarin, Floor A. M. Duijkers, Maria J. Guillen Sacoto, Erin Torti, David Geneviève, David J. Harris, Valerie Loik Ramey, Klaske D. Lichtenbelt, Arthur Sorlin, Miriam Maik, Anne Guimier, Paul Kuentz, Tatjana Bierhals, Orly Elpeleg, Yoshiko Murakami, Laurence Faivre, Jean Baptiste Rivière, Jill Clayton-Smith, Laurent Pasquier, Yuichi Abe, Edgard Verdura, Aviva Fattal, Judith St-Onge, Daphné Lehalle, Joerg Betschinger, Krista Sondergaard-Schatz, Laurie Simone, Christa W. Habela, Ivon Cusco, Mieke M. van Haelst, Pierre Vabres, Laurence Duplomb, Magali Avila, Sakoto Miyakate, Koen L.I. van Gassen, Julien Thevenon, Eveline S. J. M. de Bont, Benjamin Cogné, Pia Zacher, Silvana van Koningsbruggen, Thibaud Jouan, Irene Valenzuela, Christel Thauvin-Robinet |
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| Přispěvatelé: | Salvy-Córdoba, Nathalie, FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Génétique médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), GeneDx [Gaithersburg, MD, USA], National Center for Child Health and Development [Tokyo], University Hospital Leipzig, Manchester Centre for Genomic Medicine [Manchester, UK] (MCGM), St Mary's Hospital Manchester-Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-Faculty of Biology, Medicine and Health [Manchester, UK], University of Manchester [Manchester], Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Vall d'Hebron University Hospital [Barcelona], University Medical Center Groningen [Groningen] (UMCG), VU University Medical Center [Amsterdam], Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center [Jerusalem], Tel Aviv Sourasky Medical Center [Te Aviv], Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Boston Children's Hospital, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Brain Centre Rudolf Magnus [Utrecht], University Medical Center [Utrecht], Hackensack University Medical Center [Hackensack], Yokohama City University (YCU), Osaka University [Osaka], CHU Pontchaillou [Rennes], Johns Hopkins University School of Medicine [Baltimore], Child Health and Human Development Program [Montréal, QC, Canada], McGill University Health Center [Montreal] (MUHC), Centre Hospitalier Universitaire [Grenoble] (CHU), University Hospital Erlangen = Uniklinikum Erlangen, Department of Clinical Genetics, Academic Medical Centre, Amsterdam, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), CIBER de Enfermedades Raras (CIBERER), Kleinwachau - Saxon Epilepsy Center Radeberg, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], Friedrich Miescher Institute for Biomedical Research (FMI), Novartis Research Foundation, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MESH: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Intellectual disability TFE3 Biology [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics MESH: Intellectual Disability 03 medical and health sciences Exon 0302 clinical medicine MESH: Whole Exome Sequencing MESH: Child Genetics medicine Missense mutation Gene Genetics (clinical) Exome sequencing Pigmentary mosaicism MESH: Pathology Molecular MESH: Adolescent MESH: Humans Alternative splicing Lysosomal metabolism MESH: Child Preschool [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology MESH: Adult medicine.disease Phenotype MESH: Infant MESH: Male Storage disorder 030104 developmental biology MESH: Genes X-Linked [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics MESH: Young Adult MESH: Epilepsy MESH: Mosaicism MESH: Pigmentation Disorders MESH: Female 030217 neurology & neurosurgery |
| Zdroj: | Journal of Medical Genetics Journal of Medical Genetics, 2020, 57 (12), pp.808-819. ⟨10.1136/jmedgenet-2019-106508⟩ Journal of medical genetics, 57(12):106508, 808-819. BMJ Publishing Group Lehalle, D, Vabres, P, Sorlin, A, Bierhals, T, Avila, M, Carmignac, V, Chevarin, M, Torti, E, Abe, Y, Bartolomaeus, T, Clayton-Smith, J, Cogné, B, Cusco, I, Duplomb, L, De Bont, E, Duffourd, Y, Duijkers, F, Elpeleg, O, Fattal, A, Geneviève, D, Guillen Sacoto, M J, Guimier, A, Harris, D J, Hempel, M, Isidor, B, Jouan, T, Kuentz, P, Koshimizu, E, Lichtenbelt, K, Loik Ramey, V, Maik, M, Miyakate, S, Murakami, Y, Pasquier, L, Pedro, H, Simone, L, Sondergaard-Schatz, K, St-Onge, J, Thevenon, J, Valenzuela, I, Abou Jamra, R, Van Gassen, K, Van Haelst, M M, Van Koningsbruggen, S, Verdura, E, Whelan Habela, C, Zacher, P, Rivière, J B, Thauvin-Robinet, C, Betschinger, J & Faivre, L 2020, ' De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features ', Journal of Medical Genetics, vol. 57, no. 12, 106508, pp. 808-819 . https://doi.org/10.1136/jmedgenet-2019-106508 Journal of Medical Genetics, 57(12):106508, 808-819. BMJ Publishing Group |
| ISSN: | 0022-2593 1468-6244 |
| DOI: | 10.1136/jmedgenet-2019-106508 |
| Popis: | IntroductionPigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko’s lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on the role for lysosomal signalling in embryonic stem cell differentiation, mutations in the X-linked transcription factor 3 (TFE3) have recently been reported in five patients. Functional analysis suggested these mutations to result in ectopic nuclear gain of functions.Materials and methodsSubsequent data sharing allowed the clustering of de novo TFE3 variants identified by exome sequencing on DNA extracted from leucocytes in patients referred for syndromic ID with or without PM.ResultsWe describe the detailed clinical and molecular data of 17 individuals harbouring a de novo TFE3 variant, including the patients that initially allowed reporting TFE3 as a new disease-causing gene. The 12 females and 5 males presented with pigmentation anomalies on Blaschko’s lines, severe ID, epilepsy, storage disorder-like features, growth retardation and recognisable facial dysmorphism. The variant was at a mosaic state in at least two male patients. All variants were missense except one splice variant. Eleven of the 13 variants were localised in exon 4, 2 in exon 3, and 3 were recurrent variants.ConclusionThis series further delineates the specific storage disorder-like phenotype with PM ascribed to de novo TFE3 mutation in exons 3 and 4. It confirms the identification of a novel X-linked human condition associated with mosaicism and dysregulation within the mechanistic target of rapamycin (mTOR) pathway, as well as a link between lysosomal signalling and human development. |
| Databáze: | OpenAIRE |
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