Phenotype and X inactivation in 45,X/46,X,r(X) cases

Kathleen A. Leppig, Virginia P. Sybert, Judith L. Ross, Christopher Cunniff, Tina Trejo, Wendy H. Raskind, Christine M. Disteche

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


We studied a new series of 21 individuals mosaic for a ring X chromosome [r(X)]. Of nine individuals with mental retardation, only one had a r(X) that lacked XIST (X-inactive-specific transcript) and was not subject to X inactivation, which would explain the abnormal phenotype; the remaining eight cases had XIST on their r(X). The majority of cases (five of seven) with mental retardation had an apparently early replicating r(X); but the androgen receptor gene (AR) was methylated on one allele in five of six informative cases, including two cases with an early replicating r(X). These conflicting results on two indicators of X inactivation suggest a potential dissociation between late replication and DNA methylation in these r(X) chromosomes, which may fail to become completely silenced. Of the twelve subjects who were not mentally retarded, all had XIST present on their r(X) and most (8/10) showed a late replicating r(X), together with AR methylation in all five informative cases, indicating r(X) inactivation. Thus, the unusual phenotypic features and mental retardation associated with the presence of a r(X) cannot be explained solely on the basis of presence or absence of XIST. The r(X) in cases with mental retardation were consistently smaller than those in individuals with normal intelligence, perhaps indicating inability for small rings to undergo structural changes associated with complete X inactivation or lethality in cases with a large non-inactivated r(X). Of the Turner syndrome features present in the r(X) cases, only edema was present in a lesser frequency than in 45,X individuals. Our cases generally had a less severe phenotype than those previously reported, suggesting that reported incidences of abnormalities may be influenced by ascertainment bias, with mental retardation potentially unrelated to the presence of the r(X) in some cases.

Original languageEnglish (US)
Pages (from-to)276-284
Number of pages9
JournalAmerican Journal of Medical Genetics
Volume128 A
Issue number3
StatePublished - Jul 30 2004


  • Cytogeneties
  • Molecular analysis
  • Ring X chromosomes
  • X inactivation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Phenotype and X inactivation in 45,X/46,X,r(X) cases'. Together they form a unique fingerprint.

Cite this