title: Inheritance of skewed X chromosome inactivation in a large family with an X-linked recessive deafness syndrome.
abstract: A new X-linked recessive deafness syndrome was recently reported and mapped to Xq22 (Mohr-Tranebjaerg 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.
authors.affiliation: Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway.
authors.forename: K H
authors.initials: KH
authors.lastname: Orstavik
authors.forename: R E
authors.initials: RE
authors.lastname: Orstavik
authors.forename: K
authors.initials: K
authors.lastname: Eiklid
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
mesh_terms: D003638:Deafness / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010375:Pedigree; D014960:X Chromosome