Influence of MECP2 gene mutation and X-chromosome inactivation on the Rett syndrome phenotype

J Child Neurol. 2004 Jul;19(7):503-8. doi: 10.1177/08830738040190070501.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Child
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomes, Human, X / genetics*
  • CpG Islands
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Silencing*
  • Humans
  • Male
  • Methyl-CpG-Binding Protein 2
  • Phenotype
  • Repressor Proteins / genetics*
  • Rett Syndrome / genetics*
  • Severity of Illness Index


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