Severe phenotypes associated with inactive ring X chromosomes

Barbara R. Migeon, Margareet Ausems, Jacques Giltay, Camille Hasley-Royster, Ethan Kazi, Thomas J. Lydon, John J.M. Engelen, Gerald V. Raymond

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27 Scopus citations


Mental retardation and congenital malformations in individuals with small ring X chromosomes are often due to the functional disomy that results from failure of these chromosomes to undergo X inactivation. Such chromosomes either lack the XIST locus or do not express it. We have carried out genetic analysis of the ring X chromosomes from two girls with a 45,X/46,X,r(X) karyotype, mental retardation, and a constellation of abnormalities characteristic of the severe phenotype due to X disomy. In each case the ring X chromosome included an intact XIST locus which was expressed; the breakpoints were distal to DXS128, and therefore outside the XIC region; transcription analysis of alleles at the androgen receptor locus confirmed that these were inactive chromosomes. The characteristics of the XIST RNA were similar to the wild-type. Additional studies in cultured fibroblasts showed a second ring in a small percentage of the cells. The association of severe phenotype with an inactive X chromosome most likely reflects the presence of a second ring X chromosome which was active at least in some tissues during embryogenesis, but is no longer prominent in the tissues we analyzed.

Original languageEnglish (US)
Pages (from-to)52-57
Number of pages6
JournalAmerican Journal of Medical Genetics
Issue number1
StatePublished - Jul 3 2000

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)


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