title: Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.
abstract: A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.
authors.affiliation: Department of Medical Genetics, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukuda
authors.forename: Yushiro
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nagamitsu
authors.forename: Kenichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Jing-Ji
authors.initials: JJ
authors.lastname: Jin
authors.forename: Iori
authors.initials: I
authors.lastname: Ohmori
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohtsuka
authors.forename: Katsuko
authors.initials: K
authors.lastname: Kuwajima
authors.forename: Shoichi
authors.initials: S
authors.lastname: Endo
authors.forename: Tsuyako
authors.initials: T
authors.lastname: Iwai
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Yamagata
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Toyojiro
authors.initials: T
authors.lastname: Matsuishi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kondo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007564:Japan; D051783:Methyl-CpG-Binding Protein 2; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins