MECP2 is highly mutated in X-linked mental retardation

Hum Mol Genet. 2001 Apr 15;10(9):941-6. doi: 10.1093/hmg/10.9.941.

Abstract

Following the recent discovery that the methyl-CpG binding protein 2 (MECP2) gene located on Xq28 is involved in Rett syndrome (RTT), a wild spectrum of phenotypes, including mental handicap, has been shown to be associated with mutations in MECP2. These findings, with the compelling genetic evidence suggesting the presence in Xq28 of additional genes besides RabGDI1 and FMR2 involved in non-specific X-linked mental retardation (MRX), prompted us to investigate MECP2 in MRX families. Two novel mutations, not found in RTT, were identified. The first mutation, an E137G, was identified in the MRX16 family, and the second, R167W, was identified in a new mental retardation (MR) family shown to be linked to Xq28. In view of these data, we screened MECP2 in a cohort of 185 patients found negative for the expansions across the FRAXA CGG repeat and reported the identification of mutations in four sporadic cases of MR. One of the mutations, A140V, which we found in two patients, has been described previously, whereas the two others, P399L and R453Q, are novel mutations. In addition to the results demonstrating the involvement of MECP2 in MRX, this study shows that the frequency of mutations in MECP2 in the mentally retarded population screened for the fragile X syndrome is comparable to the frequency of the CGG expansions in FMR1. Therefore, implementation of systematic screening of MECP2 in MR patients should result in significant progress in the field of molecular diagnosis and genetic counseling of mental handicap.

Publication types

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

MeSH terms

  • Adult
  • Base Sequence
  • Chromosomal Proteins, Non-Histone*
  • CpG Islands / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Fragile X Mental Retardation Protein
  • Genetic Linkage*
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Methyl-CpG-Binding Protein 2
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Nerve Tissue Proteins / genetics
  • Pedigree
  • RNA-Binding Proteins*
  • Repressor Proteins / genetics
  • Rett Syndrome / genetics
  • Sex Factors
  • X Chromosome / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • FMR1 protein, human
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • Fragile X Mental Retardation Protein

Associated data

  • GENBANK/X99686