Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation

Hum Mutat. 2001 Sep;18(3):253. doi: 10.1002/humu.1186.


Rett syndrome is an X-linked dominant neurodevelopmental disorder that affects females almost exclusively. The recent identification of mutations of the methyl-CpG-binding protein 2 gene (MECP2) in patients with RTT, encouraged us to analyze the gene in 37 Japanese patients divided into classical RTT (14 cases), variant RTT (13 cases), and mentally retarded patients with Rett-like features (10 cases). Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases). Six reported common mutations were detected in 17 cases, and rare single nucleotide substitutions were found in 3 patients. In addition, one insertion mutation (1189insA) and four deletion mutations including one double deletion mutant (451delG, 100del4, 1124del53 and 881del289 plus 1187del8) were newly identified. In the 10 mentally retarded patients with Rett-like features, however, no mutation was detected in the coding region of MECP2. The finding of MECP2 mutations in 92.5% of patients with RTT indicates that RTT fulfilling the diagnostic criteria are due to genetic alteration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Chromosomal Proteins, Non-Histone*
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Genotype
  • Humans
  • Japan
  • Male
  • Methyl-CpG-Binding Protein 2
  • Mutagenesis, Insertional
  • Mutation
  • Phenotype
  • Point Mutation
  • Repressor Proteins*
  • Rett Syndrome / genetics*
  • Rett Syndrome / pathology
  • Sequence Deletion


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins
  • DNA