title: The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation.
abstract: Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45,X/46,X,r(X) karyotype. Studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed. As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia, nonexpression of the locus even when it is present suggests that these chromosomes are transcriptionally active. We examined the transcriptional activity of ring X chromosomes lacking XIST expression (XISTE-), from three females with severe phenotypes. The two tiny ring X chromosomes studied with an antibody specific for the acetylated isoforms of histone H4 marking transcribed chromatin domains were labeled at a level consistent with their being active. We also examined tow of the XISTE- ring chromosomes to determine whether genes that are normally silent on an inactive X are expressed from these chromosomes. Analyses of hybrid cells show that TIMP, ZXDA, and ZXDB loci on the proximal short arm, and AR and PHKA1 loci on the long arm, are well expressed from the tiny ring X chromosome lacking XIST DNA. Studies of the ring chromosome that has XIST DNA but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Center for Medical Genetics, Johns Hopkins University, Baltimore.
authors.forename: B R
authors.initials: BR
authors.lastname: Migeon
authors.forename: S
authors.initials: S
authors.lastname: Luo
authors.forename: M
authors.initials: M
authors.lastname: Jani
authors.forename: P
authors.initials: P
authors.lastname: Jeppesen
mesh_terms: D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D008214:Lymphocytes; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D010764:Phosphorylase Kinase / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000032:analysis; D022661:RNA, Untranslated; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics; D012303:Ring Chromosomes; D019714:Tissue Inhibitor of Metalloproteinases; D014157:Transcription Factors / Q000172:deficiency*; D014158:Transcription, Genetic; D014424:Turner Syndrome / Q000235:genetics* / Q000473:pathology; D014960:X Chromosome / Q000473:pathology*; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D017931:DNA Primers; D006023:Glycoproteins; D006657:Histones; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D011944:Receptors, Androgen; D019714:Tissue Inhibitor of Metalloproteinases; D014157:Transcription Factors; C077885:XIST non-coding RNA; D010764:Phosphorylase Kinase