X chromosome inactivation and X-linked mental retardation.


Journal Article (Review)

The expression of X-linked genes in females heterozygous for X-linked defects can be modulated by epigenetic control mechanisms that constitute the X chromosome inactivation pathway. At least four different effects have been found to influence, in females, the phenotypic expression of genes responsible for X-linked mental retardation (XLMR). First, non-random X inactivation, due either to stochastic or genetic factors, can result in tissues in which one cell type (for example, that in which the X chromosome carrying a mutant XLMR gene is active) dominates, instead of the normal mosaic cell population expected as a result of random X inactivation. Second, skewed inactivation of the normal X in individuals carrying a deletion of part of the X chromosome has been documented in a number of mentally retarded females. Third, functional disomy of X-linked genes that are expressed inappropriately due to the absence of X inactivation has been found in mentally retarded females with structurally abnormal X chromosomes that do not contain the X inactivation center. And fourth, dose-dependent overexpression of X-linked genes that normally "escape" X inactivation may account for the mental and developmental delay associated with increasing numbers of otherwise inactive X chromosomes in individuals with X chromosome aneuploidy.

Full Text

Cited Authors

  • Willard, HF

Published Date

  • July 1996

Published In

Volume / Issue

  • 64 / 1

Start / End Page

  • 21 - 26

PubMed ID

  • 8826443

Pubmed Central ID

  • 8826443

Electronic International Standard Serial Number (EISSN)

  • 1096-8628

International Standard Serial Number (ISSN)

  • 0148-7299

Digital Object Identifier (DOI)

  • 10.1002/(sici)1096-8628(19960712)64:1<21::aid-ajmg2>3.0.co;2-u


  • eng