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Lack of X inactivation associated with maternal X isodisomy: evidence for a counting mechanism prior to X inactivation during human embryogenesis.
- Source :
-
American journal of human genetics [Am J Hum Genet] 1996 Jan; Vol. 58 (1), pp. 161-70. - Publication Year :
- 1996
-
Abstract
- We have previously reported functional disomy for X-linked genes in females with tiny ring X chromosomes and a phenotype significantly more abnormal than Turner syndrome. In such cases the disomy results from failure of these X chromosomes to inactivate because they lack DNA sequences essential for cis X inactivation. Here we describe a novel molecular mechanism for functional X disomy that is associated with maternal isodisomy. In this case, the severe mental retardation and multiple congenital abnormalities in a female with a mosaic 45,X/ 46,X,del(X)(q21.3-qter)/ 46X,r(X) karyotype are associated with overexpression of the genes within Xpter to Xq21.31 in many of her cells. Her normal X, ring X, and deleted linear X chromosomes originate from the same maternal X chromosome, and all are transcriptionally active. None expresses X inactive specific transcript (XIST), although the locus and region of the putative X inactivation center (XIC) are present on both normal and linear deleted X chromosomes. To our knowledge, this is the first report of a functional maternal X isodisomy, and the largest X chromosome to escape inactivation. In addition, these results (1) show that cis inactivation does not invariably occur in human females with two X chromosomes, even when the XIC region is present on both of them; (2) provide evidence for a critical time prior to the visible onset of X inactivation in the embryo when decisions about X inactivation are made; and (3) support the hypothesis that the X chromosome counting mechanism involves chromosomal imprinting, occurs prior to the onset of random inactivation, and is required for subsequent inactivation of the chromosome.
- Subjects :
- Cell Division
Cells, Cultured
Child
Chromosome Mapping
DNA Replication
Female
Genetic Markers
Humans
Hybrid Cells
In Situ Hybridization, Fluorescence
Karyotyping
Male
Mosaicism
Polymerase Chain Reaction
Pregnancy
Transcription, Genetic
Turner Syndrome metabolism
Chromosome Deletion
Embryonic and Fetal Development genetics
Ploidies
Sex Chromosome Aberrations
Turner Syndrome genetics
X Chromosome
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9297
- Volume :
- 58
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 8554052