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Inheritance of skewed X chromosome inactivation in a large family with an X-linked recessive deafness syndrome

Journal Article · · American Journal of Medical Genetics
; ;  [1];  [2]
  1. Ulleval Univ. Hospital, Oslo (Norway)
  2. Univ. Hospital, Tromso (Norway)
A new X-linked recessive deafness syndrome was recently reported and mapped to Xq22 (Mohr-Tranebjaeerg syndrome). In addition to deafness, the patients had visual impairment, dystonia, fractures, and mental deterioration. The female carriers did not have any significant manifestations of the syndrome. We examined X chromosome inactivation in 8 obligate and 12 possible carriers by using a polymerase chain reaction analysis of the methylation-dependent amplification of the polymorphic triplet repeat at the androgen receptor locus. Seven of 8 obligate carriers and 1 of 5 carriers by linkage analysis had an extremely skewed pattern in blood DNA not found in 30 normal females. The X inactivation pattern in fibroblast DNA from 2 of the carriers with the extremely skewed pattern was also skewed but to a lesser degree than in blood DNA. One obligate carrier had a random X inactivation pattern in both blood and fibroblast DNA. A selection mechanism for the skewed pattern is therefore not likely. The extremely skewed X inactivation in 8 females of 3 generations in this family may be caused by a single gene that influences skewing of X chromosome inactivation. 22 refs., 2 figs., 1 tab.
OSTI ID:
476904
Journal Information:
American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 1 Vol. 64; ISSN 0148-7299; ISSN AJMGDA
Country of Publication:
United States
Language:
English