| Autor: |
Migeon BR; Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21287-3914, USA., Jeppesen P, Torchia BS, Fu S, Dunn MA, Axelman J, Schmeckpeper BJ, Fantes J, Zori RT, Driscoll DJ |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of human genetics [Am J Hum Genet] 1996 Jan; Vol. 58 (1), pp. 161-70. |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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