SKEWED X-CHROMOSOME INACTIVATION IN FEMALE CARRIERS OF DYSKERATOSIS-CONGENITA

In this study, we report on a family with X-linked dyskeratosis congen ita (DC). Linkage analysis with markers in the factor Vm gene at Xq28 yielded a LOD score of 2 at a recombination of O. Clinical manifestati ons of DC, such as skin lesions following the Blaschko lines, were pre sent in two obligate carrier females. Highly skewed X inactivation was observed in white blood cells, cultured skin fibroblasts, and buccal mucosa from female carriers of DC in this family. This suggests a crit ical role for the DC gene in bone marrow-cell and fibroblast-cell prol iferation.