Severe phenotypes associated with inactive ring X chromosomes.
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.
Migeon
B R
BR
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21287-3914, USA. bmigeon@welch.jhu.edu
Ausems
M
M
Giltay
J
J
Hasley-Royster
C
C
Kazi
E
E
Lydon
T J
TJ
Engelen
J J
JJ
Raymond
G V
GV
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
D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D011944:Receptors, Androgen; D014157:Transcription Factors; C077885:XIST non-coding RNA