Abstract

Aim: Dyskeratosis congenita (DC) is characterised by the failure of those tissues that are rapidly dividing in the adult, particularly the skin, mucosae, and haemopoietic system. The X linked form of the disease is caused by mutations of the DKC1 gene, which encodes dyskerin, a protein that is necessary for the function of telomerase. Cultured DC lymphoblastoid cells are characterised by a reduced expansion of the cell population because of the progressive increase in apoptosis compared with the number of cell divisions. This report aimed to verify whether this is caused by a defect in telomerase function.

Methods: Variations in telomere length over time were evaluated in two cultured lymphoblastoid cell lines derived from patients with X linked DC and control cells derived from a non-affected individual. In addition, the effect of inhibiting poly (ADP-ribose) polymerase (PARP), which is involved in the cellular response to excessive telomere shortening, was assessed. One DC cell line and the control cells were treated with the specific PARP inhibitor 1,5-dihydroxyquinoline (IQ).

Results: In DC cells the increase in cell death was associated with progressive telomere shortening, and this was not seen in the control cells. Treatment with IQ delayed the increase of apoptosis in DC cells.

Conclusions: These observations indicate that the reduced expansion that characterises cultured cells obtained from patients with X linked DC is caused by premature telomere shortening.