Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome in which patients undergo premature ageing and have a predisposition to malignancy. X-linked and autosomal (dominant and recessive) forms of the disease are recognized. The gene responsible for X-linked DC (DKC1) encodes a highly conserved protein called dyskerin that is believed to be essential in ribosome biogenesis and may also be involved in telomerase RNP assembly. Here we show that in X-linked DC, peripheral blood cells have dramatically reduced telomere lengths but normal levels of telomerase activity. We also find that subjects with autosomal DC have significantly shorter telomeres than age-matched normal controls suggesting that both forms of the disease are associated with rapid telomere shortening in hemopoietic stem cells. The further characterization of these genes will not only lead to a better understanding of the biology of DC but may also provide further insights into the maintenance of telomeres and the biology of aplastic anemia, ageing, and cancer.
Copyright 2001 Academic Press.