Loss-of-Function Mutation in the Dioxygenase-Encoding FTO Gene Causes Severe Growth Retardation and Multiple Malformations
| Autor: | Christelle Golzio, Tomas Lindahl, Hiroko Kawagoe-Takaki, Laurence Colleaux, Giles S.H. Yeo, Stephen O'Rahilly, I. Sadaf Farooqi, Noman Kadhom, Orit Reish, Philippe Froguel, Heather C. Etchevers, Vladimir Saudek, Sarah Boissel, David Meyre, Florence Molinari, Karine Proulx, Barbara Sedgwick, Arnold Munnich |
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| Přispěvatelé: | Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology and Molecular Medicine [Hamilton, ON, Canada], McMaster University [Hamilton, Ontario], IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clare Hall Laboratories, Cancer Research UK-London Res Inst, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Senescence
medicine.medical_specialty endocrine system diseases Molecular Sequence Data Alpha-Ketoglutarate-Dependent Dioxygenase FTO Biology medicine.disease_cause FTO gene 03 medical and health sciences 0302 clinical medicine Dioxygenase Report Internal medicine Genetics medicine Animals Humans Abnormalities Multiple Genetic Predisposition to Disease Genetics(clinical) Amino Acid Sequence Nuclear protein Gene Growth Disorders Genetics (clinical) 030304 developmental biology 0303 health sciences Mutation Intron Proteins nutritional and metabolic diseases pathological conditions signs and symptoms Pedigree Endocrinology [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Sequence Alignment 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Human Genetics American Journal of Human Genetics, Elsevier (Cell Press), 2009, 85 (1), pp.106-111. ⟨10.1016/j.ajhg.2009.06.002⟩ American Journal of Human Genetics, 2009, 85 (1), pp.106-111. ⟨10.1016/j.ajhg.2009.06.002⟩ |
| ISSN: | 0002-9297 1537-6605 |
| DOI: | 10.1016/j.ajhg.2009.06.002⟩ |
| Popis: | International audience; FTO is a nuclear protein belonging to the AlkB-related non-haem iron-and 2-oxoglutarate-dependent dioxygenase family. Although polymorphisms within the first intron of the FTO gene have been associated with obesity, the physiological role of FTO remains unknown. Here we show that a R316Q mutation, inactivating FTO enzymatic activity, is responsible for an autosomal-recessive lethal syndrome. Cultured skin fibroblasts from affected subjects showed impaired proliferation and accelerated senescence. These findings indicate that FTO is essential for normal development of the central nervous and cardiovascular systems in human and establish that a mutation in a human member of the AlkB-related dioxygenase family results in a severe polymalformation syndrome. |
| Databáze: | OpenAIRE |
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