title: Expanding phenotype of p.Ala140Val mutation in MECP2 in a 4 generation family with X-linked intellectual disability and spasticity.
abstract: Mutations in MECP2 (MIM #312750), located on Xq28 and encoding a methyl CpG binding protein, are classically associated with Rett syndrome in female patients, with a lethal effect in hemizygous males. However, MECP2 mutations have already been reported in surviving males with severe neonatal-onset encephalopathy, or with X-linked intellectual disability associated with psychosis, pyramidal signs, parkinsonian features and macro-orchidism (PPM-X syndrome; MIM3 #300055). Here we report on the identification of the p.Ala140Val mutation in the MECP2 gene in 4 males and 3 females of a large Caucasian family affected with X-linked intellectual disability. Females present with mild cognitive impairment and speech difficulties. Males have moderate intellectual disability, impaired language development, friendly behavior, slowly progressive spastic paraparesis and dystonic movements of the hands. Two of them show microcephaly. The p.Ala140Val mutation is recurrent, as it was already described in 4 families with X-linked mental retardation and in three sporadic male patients with intellectual disability. We further delineate the phenotype associated with the p.Ala140Val mutation, illustrating a variable expressivity even within a given family, and we compare our patients with previous reported cases in the literature.
authors.affiliation: Department of Pediatrics, Université Catholique de Louvain (U.C.L.), Brussels, Belgium; Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lambert
authors.affiliation: Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium; Faculty of Medicine, Université Namur (U.N.), Namur, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maystadt
authors.affiliation: Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Boulanger
authors.affiliation: Department of Neurology, Hôpital de Jolimont, Haine-saint-Paul, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: Vrielynck
authors.affiliation: Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Destrée
authors.affiliation: Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Lederer
authors.affiliation: Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium. Electronic address: stephanie.moortgat@ipg.be.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Moortgat
mesh_terms: D000328:Adult; D000368:Aged; D001259:Ataxia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D004827:Epilepsy / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D038901:X-Linked Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008831:Microcephaly / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D009128:Muscle Spasticity / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D015835:Ocular Motility Disorders / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D015518:Rett Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: Angelman-like phenotype; MECP2 gene; PPM-X syndrome; Rett syndrome; X-linked intellectual disability