title: Semi-dominant X-chromosome linked learning disability with progressive ataxia, spasticity and dystonia associated with the novel MECP2 variant p.V122A: akin to the new MECP2 duplication syndrome?
abstract: A novel X-chromosome linked phenotype is reported. Three affected males had learning disability in early childhood and subsequently developed progressive ataxia, dystonia, and spasticity with death at ages 9, 14 and 19 years. Two female obligate carriers had learning difficulties with psychosis in one case. A third, possible carrier had learning difficulties and epilepsy. A family study indicates that this inherited syndrome is most likely due to an unreported MECP2 variant, p.V122A, located in the methyl binding domain of the MECP2 protein. The clinical features are similar to those present in the newly reported MECP2 duplication syndrome. Non-progressive neuropsychiatric symptoms in female relatives of a male child with learning disability, ataxia and progressive spasticity may constitute a clue to inherited, MECP2 pathogenesis.
authors: West of Scotland Regional Genetics Service, Yorkhill Hospitals, Glasgow G3 8 SJ, UK.
authors: Catherine
authors: C
authors: McWilliam
authors: A
authors: A
authors: Cooke
authors: D
authors: D
authors: Lobo
authors: J
authors: J
authors: Warner
authors: M
authors: M
authors: Taylor
authors: J L
authors: JL
authors: Tolmie
mesh_terms: D000293:Adolescent; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D004421:Dystonia / Q000235:genetics / Q000503:physiopathology; D017809:Fatal Outcome; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology; D009128:Muscle Spasticity / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D055815:Young Adult
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2