title: Influence of MECP2 gene mutation and X-chromosome inactivation on the Rett syndrome phenotype.
abstract: To date, approximately 200 different mutations in the MECP2 gene have been identified. We analyzed the entire coding sequence of the MECP2 gene and the X-chromosome inactivation pattern in 42 sporadic cases of Rett syndrome. Of the 42 patients, 30 had pathogenic mutations, including 14 different mutations: 9 missense mutations, 4 nonsense mutations, and 1 frameshift mutation. One was a novel mutation (S134P). There was a tendency for patients who had a nonsense mutation in the transcriptional repression domain region to show earlier onset of regression and more severe language retardation than patients with a mutation in the methyl-CpG binding domain region. However, the parameters of clinical severity were variable among patients with the same type of mutation, depending on the pattern of X-chromosome inactivation. This study suggests that the X-chromosome inactivation pattern can modify the phenotype of Rett syndrome, which is primarily determined by the type and site of MECP2 gene mutation.
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, 28 Yongon-dong, Jongnogu, Seoul 110-744, Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chae
authors.forename: Hee
authors.initials: H
authors.lastname: Hwang
authors.forename: Yong Seung
authors.initials: YS
authors.lastname: Hwang
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Cheong
authors.forename: Ki Joong
authors.initials: KJ
authors.lastname: Kim
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D018899:CpG Islands; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins