Association between aplastic anaemia and mutations in telomerase RNA.

The main cause of aplastic anaemia remains elusive. Germline mutations in the gene encoding the RNA component of telomerase (hTR) have been seen in the autosomal dominant form of dyskeratosis congenita--an inherited syndrome characterised by aplastic anaemia. By screening the hTR gene, we identified mutations in two of 17 patients with idiopathic aplastic anaemia, three of 27 patients with constitutional aplastic anaemia, but in none of 214 normal controls (p<0.0001). Furthermore, patients with hTR mutations had significantly shorter telomeres than age-matched controls (p=0.027). These data indicate that, in a subset of patients with aplastic anaemia, the disorder might be associated with a genetic lesion in the telomere maintenance pathway.