INHERITANCE OF SKEWED X-CHROMOSOME INACTIVATION IN A LARGE FAMILY WITH AN X-LINKED RECESSIVE DEAFNESS SYNDROME

A new X-linked recessive deafness syndrome was recently reported and m apped to Xq22 (Mohr-Tranebjaerg syndrome), In addition to deafness, th e patients had visual impairment, dystonia, fractures, and mental dete rioration, The female carriers did not have any significant manifestat ions of the syndrome, We examined X chromosome inactivation in 8 oblig ate and 12 possible carriers by using a polymerase chain reaction anal ysis of the methylation-dependent amplification of the polymorphic tri plet repeat at the androgen receptor locus. Seven of 8 obligate carrie rs and 1 of 5 carriers by linkage analysis had an extremely skewed pat tern in blood DNA not found in 30 normal females, The X inactivation p attern in fibroblast DNA from 2 of the carriers with the extremely ske wed 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 t herefore not likely, The extremely skewed X inactivation in 8 females of 3 generations in this family may be caused by a single gene that in fluences skewing of X chromosome inactivation. (C) 1996 Wiley-Liss, In c.