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

Research output: Contribution to journalArticle

Abstract

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
Volume93
Issue number1
StatePublished - Jul 3 2000

Fingerprint

Ring Chromosomes
X Chromosome
Phenotype
Chromosomes
Intellectual Disability
X Chromosome Inactivation
Androgen Receptors
Karyotype
Embryonic Development
Fibroblasts
Alleles
RNA

Keywords

  • Inactive r(X)
  • Mental retardation
  • Parental origin of ring X chromosomes
  • Ring X chromosome
  • Severe phenotype
  • Turner syndrome
  • XIST

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Migeon, B. R., Ausems, M., Giltay, J., Hasley-Royster, C., Kazi, E., Lydon, T. J., ... Raymond, G. V. (2000). Severe phenotypes associated with inactive ring X chromosomes. American Journal of Medical Genetics, 93(1), 52-57.

Severe phenotypes associated with inactive ring X chromosomes. / Migeon, Barbara R; Ausems, Margareet; Giltay, Jacques; Hasley-Royster, Camille; Kazi, Ethan; Lydon, Thomas J.; Engelen, John J M; Raymond, Gerald V.

In: American Journal of Medical Genetics, Vol. 93, No. 1, 03.07.2000, p. 52-57.

Research output: Contribution to journalArticle

Migeon, BR, Ausems, M, Giltay, J, Hasley-Royster, C, Kazi, E, Lydon, TJ, Engelen, JJM & Raymond, GV 2000, 'Severe phenotypes associated with inactive ring X chromosomes', American Journal of Medical Genetics, vol. 93, no. 1, pp. 52-57.
Migeon BR, Ausems M, Giltay J, Hasley-Royster C, Kazi E, Lydon TJ et al. Severe phenotypes associated with inactive ring X chromosomes. American Journal of Medical Genetics. 2000 Jul 3;93(1):52-57.
Migeon, Barbara R ; Ausems, Margareet ; Giltay, Jacques ; Hasley-Royster, Camille ; Kazi, Ethan ; Lydon, Thomas J. ; Engelen, John J M ; Raymond, Gerald V. / Severe phenotypes associated with inactive ring X chromosomes. In: American Journal of Medical Genetics. 2000 ; Vol. 93, No. 1. pp. 52-57.
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