Mutation analysis of the MECP2 gene in British and Italian Rett syndrome females

J Mol Med (Berl). 2001;78(11):648-55. doi: 10.1007/s001090000155.


Rett syndrome is an X-linked dominant neurological disorder, which appears to be the commonest genetic cause of profound combined intellectual and physical disability in Caucasian females. Recently, this syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of still unknown target genes. Here we report a detailed mutational analysis of 62 patients from UK and Italian archives, representing the first comparative study among different populations and one of the largest number of cases so far analyzed. We review the literature on MECP2 mutations in Rett syndrome. This analysis has permitted us to produce a map of the recurrent mutations identified in this and previous studies. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, which is conserved among brain-specific regulatory factors.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone*
  • Conserved Sequence
  • DNA Mutational Analysis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Evolution, Molecular
  • Exons
  • Female
  • Frameshift Mutation
  • Heterozygote
  • Humans
  • Infant
  • Introns
  • Italy
  • Methyl-CpG-Binding Protein 2
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Mutation, Missense
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Protein Structure, Tertiary
  • Repressor Proteins*
  • Rett Syndrome / ethnology*
  • Rett Syndrome / genetics*
  • Sequence Homology, Amino Acid
  • United Kingdom


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

Grants and funding