title: Severe phenotypes associated with inactive ring X chromosomes.
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.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21287-3914, USA. bmigeon@welch.jhu.edu
authors.forename: B R
authors.initials: BR
authors.lastname: Migeon
authors.forename: M
authors.initials: M
authors.lastname: Ausems
authors.forename: J
authors.initials: J
authors.lastname: Giltay
authors.forename: C
authors.initials: C
authors.lastname: Hasley-Royster
authors.forename: E
authors.initials: E
authors.lastname: Kazi
authors.forename: T J
authors.initials: TJ
authors.lastname: Lydon
authors.forename: J J
authors.initials: JJ
authors.lastname: Engelen
authors.forename: G V
authors.initials: GV
authors.lastname: Raymond
mesh_terms: D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D007223:Infant; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated; D011944:Receptors, Androgen / Q000235:genetics; D012303:Ring Chromosomes; D014157:Transcription Factors / Q000235:genetics; D014960:X Chromosome
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D011944:Receptors, Androgen; D014157:Transcription Factors; C077885:XIST non-coding RNA