title: Skewed X chromosome inactivation failed to explain the normal phenotype of a carrier female with MECP2 mutation resulting in Rett syndrome.
abstract: Mutations in the X-linked MECP2 gene cause Rett syndrome, a neurodevelopmental disorder that exclusively affects girls. Females with the MECP2 mutations exhibit a broad spectrum of clinical presentations ranging from classical Rett syndrome to asymptomatic carriers, which can be explained by differences in X chromosome inactivation (XCI). Here, we report a family with a girl with Rett syndrome in whom a novel missense mutation in the MECP2 gene was transmitted through the maternal germ line. The carrier mother was asymptomatic and presented non-random XCI in the peripheral blood cells, which resulted in the X chromosome harboring the mutant allele that was predominantly active. Thus, the presence of non-random XCI in the peripheral blood cells did not provide an explanation for the normal phenotype of the carrier mother. This result suggests that mechanisms other than XCI may contribute to the phenotypic heterogeneity associated with MECP2 mutations.
authors.affiliation: Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan. satoru5p@asahikawa-med.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: J
authors.initials: J
authors.lastname: Ohinata
authors.forename: Y
authors.initials: Y
authors.lastname: Makita
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Araki
authors.forename: A
authors.initials: A
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Murono
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Fujieda
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D051783:Methyl-CpG-Binding Protein 2; D050505:Mutant Proteins