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


Journal Article

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.

Full Text

Cited Authors

  • Plenge, RM; Stevenson, RA; Lubs, HA; Schwartz, CE; Willard, HF

Published Date

  • July 2002

Published In

Volume / Issue

  • 71 / 1

Start / End Page

  • 168 - 173

PubMed ID

  • 12068376

Pubmed Central ID

  • 12068376

Electronic International Standard Serial Number (EISSN)

  • 1537-6605

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/341123


  • eng