MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations.: MEF2C haploinsufficiency
| Autor: | Joris Andrieux, Véronique David, Dominique Bonneau, Magalie Barth, Hubert Journel, Muriel Holder-Espinasse, Alice Goldenberg, Sylvie Jaillard, Aude Charollais, Thierry Frebourg, Nathalie Le Meur, Cécile Boucher, Sylvie Manouvrier-Hanu, Christèle Dubourg, Stéphane Auvin, Agnès Guichet, Sylvie Joriot, Pascale Saugier-Veber, Jean-Pierre Kerckaert, Patrizia Amati-Bonneau |
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| Přispěvatelé: | Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de Cytogénétique, Etablissement français du sang - Normandie (EFS), Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Neuropédiatrie, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Génétique Médicale, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA)-Hôpital Chubert, Service de neurologie pédiatrique et maladies métaboliques, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de Génomique Fonctionnelle, Université de Lille, Droit et Santé, Service de biologie moléculaire, Hôpital Pontchaillou, Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7) |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Cerebrum
Haploidy Epilepsy 0302 clinical medicine MESH: Child MESH: Mental Retardation MEF2C Child [SDV.BDD]Life Sciences [q-bio]/Development Biology Genetics (clinical) seizures Genetics 0303 health sciences MEF2 Transcription Factors MESH: Myogenic Regulatory Factors MESH: Haploidy MESH: Stereotypic Movement Disorder MESH: Infant Hypotonia Stereotypic movement disorder Myogenic Regulatory Factors Child Preschool MESH: Epilepsy Chromosomes Human Pair 5 Medical genetics Chromosome Deletion medicine.symptom Haploinsufficiency MESH: Chromosomes Human Pair 5 medicine.medical_specialty MESH: Chromosome Deletion 5q14.3 microdeletion Nonsense mutation Stereotypic Movement Disorder MADS Domain Proteins Biology mental retardation Article MESH: MADS Domain Proteins 03 medical and health sciences Intellectual Disability medicine Humans Cerebrum 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics MESH: Humans MESH: Child Preschool Infant medicine.disease Developmental disorder array-CGH 030217 neurology & neurosurgery |
| Zdroj: | Journal of Medical Genetics Journal of Medical Genetics, BMJ Publishing Group, 2010, 47 (1), pp.22-9. ⟨10.1136/jmg.2009.069732⟩ Journal of Medical Genetics, 2010, 47 (1), pp.22-9. ⟨10.1136/jmg.2009.069732⟩ |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | International audience; BACKGROUND: Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. METHOD: Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. RESULTS: 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. CONCLUSION: Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations. |
| Databáze: | OpenAIRE |
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