Analysis of the parental origin of de novo MECP2 mutations and X chromosome inactivation in 24 sporadic patients with Rett syndrome in China

J Child Neurol. 2010 Jul;25(7):842-8. doi: 10.1177/0883073809350722. Epub 2010 Mar 5.

Abstract

Rett syndrome is an X-linked neurodevelopmental disorder that predominantly affects females. It is caused by mutations in methyl-CpG-binding protein 2 gene. Due to the sex-limited expression, it has been suggested that de novo X-linked mutations may exclusively occur in male germ cells and thus only females are affected. In this study, the authors have analyzed the parental origin of mutations and the X-chromosome inactivation status in 24 sporadic patients with identified methyl-CpG-binding protein 2 gene mutations. The results showed that 22 of 24 patients have a paternal origin. Only 2 patients have a maternal origin. Except for 2 cases which were homozygotic at the androgen receptor gene locus, of the remaining 22 cases, 16 cases have a random X-chromosome inactivation pattern; the other 6 cases have a skewed X-chromosome inactivation and they favor expression of the wild allele. The relationship between X-chromosome inactivation and phenotype may need more cases to explore.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Asian People / genetics*
  • Child, Preschool
  • DNA Mutational Analysis
  • Fathers
  • Female
  • Humans
  • Infant
  • Membrane Glycoproteins
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Mothers
  • Mutation*
  • Parents*
  • Phenotype
  • Polymerase Chain Reaction
  • Receptors, Interleukin-1
  • Rett Syndrome / genetics*
  • X Chromosome Inactivation*

Substances

  • MECP2 protein, human
  • Membrane Glycoproteins
  • Methyl-CpG-Binding Protein 2
  • Receptors, Interleukin-1
  • TIRAP protein, human