SKEWED X-INACTIVATION IN CARRIERS OF X-LINKED DYSKERATOSIS-CONGENITA

gene causing Dyskeratosis Congenita (DC), a rare genetic disorder asso ciated with bone marrow failure, has been mapped to chromosome Xq28, b ut autosomal inheritance of the disease has also been reported. We hav e investigated the pattern of X-inactivation in the peripheral brood o f carriers of DC using the methylation-sensitive Hpa II site in the an drogen receptor gene (HUMARA). In 5 different families in which the in heritance of DC appears to be X-linked, all 16 carriers showed skewed X-inactivation patterns. These cases indicate that, in the hematopoies is of heterozygous females, cells expressing the normal DC allele have a growth advantage over cells that express the mutant allele. In 7 ot her families with sporadic cases of DC or with an uncertain pattern of inheritance, both skewed and normal patterns of X-inactivation were o bserved. In these families or where crucial family members are unavail able, the study of X-inactivation patterns will add to linkage analysi s in providing information about carrier status. (C) 1997 by The Ameri can Society of Hematology.