Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders

Am J Hum Genet. 2002 Jul;71(1):168-73. doi: 10.1086/341123. Epub 2002 May 30.


Some deleterious X-linked mutations may result in a growth disadvantage for those cells in which the mutation, when on the active X chromosome, affects cell proliferation or viability. To explore the relationship between skewed X-chromosome inactivation and X-linked mental retardation (XLMR) disorders, we used the androgen receptor X-inactivation assay to determine X-inactivation patterns in 155 female subjects from 24 families segregating 20 distinct XLMR disorders. Among XLMR carriers, approximately 50% demonstrate markedly skewed X inactivation (i.e., patterns > or =80:20), compared with only approximately 10% of female control subjects (P<.001). Thus, skewed X inactivation is a relatively common feature of XLMR disorders. Of the 20 distinct XLMR disorders, 4 demonstrate a strong association with skewed X inactivation, since all carriers of these mutations demonstrate X-inactivation patterns > or =80:20. The XLMR mutations are present on the preferentially inactive X chromosome in all 20 informative female subjects from these families, indicating that skewing is due to selection against those cells in which the XLMR mutation is on the active X chromosome.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Case-Control Studies
  • Dosage Compensation, Genetic*
  • Female
  • Genetic Linkage*
  • Heterozygote
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Mutation
  • Pedigree
  • Receptors, Androgen / genetics


  • Receptors, Androgen