Very short telomeres in the peripheral blood of patients with X-linked andautosomal dyskeratosis congenita

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome in which patients undergo premature ageing and have a predisposition to malig nancy. X-linked and autosomal (dominant and recessive) forms of the disease are recognized. The gene responsible for X-linked DC (DKCI) encodes a high ly conserved protein called dyskerin that is believed to be essential in ri bosome biogenesis and may also be involved in telomerase RNP assembly. Here we show that in X-linked DC, peripheral blood cells have dramatically redu ced 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 a ssociated with rapid telomere shortening in hemopoietic stem cells. The fur ther characterization of these genes will not only lead to a better underst anding of the biology of DC but may also provide further insights into the maintenance of telomeres and the biology of aplastic anemia, ageing, and ca ncer (C) 2001 Academic Press.