X INACTIVATION ANALYSIS IN A FEMALE WITH HYPOMELANOSIS OF ITO ASSOCIATED WITH A BALANCED X-17 TRANSLOCATION - EVIDENCE FOR FUNCTIONAL DISOMY OF XP

X inactivation analysis was performed on normal and hypopigmented skin samples obtained from a female with hypomelanosis of Ito associated w ith a balanced whole arm X;17 translocation. Severe skewing of X inact ivation resulting in inactivity of the intact X was found in blood and cultures of both types of skin, but analysis of DNA prepared directly from hypopigmented skin showed significant inactivation of the transl ocated X, inconsistent with the usual mechanism of phenotypic expressi on in X;autosome translocations. In addition, dual colour FISH analysi s using centromere specific probes for chromosomes X and 17 showed tha t the breakpoints on both chromosomes lie within the alphoid arrays, m aking interruption of a locus on either chromosome unlikely. While par tial variable monosomy of loci on chromosome 17p cannot be excluded as contributing to the phenotype in this patient, it is argued that the major likely factor is partial functional disomy of sequences on Xp in cell lineages that have failed to inactivate the intact X chromosome.