Impact of germline CTC 1 alterations on telomere length in acquired bone marrow failure

Compound heterozygous germline mutations in CTC 1 gene have been found in patients with atypical dyskeratosis congenita ( DC ), whereas heterozygous carriers are unaffected. Through screening of a large cohort of adult patients with acquired bone marrow failure syndromes, in addition to a DC case, we have also found extremely rare or novel heterozygous deleterious germline variants of CTC 1 in patients with aplastic anaemia ( AA ; n = 5), paroxysmal nocturnal haemoglobinuria (PNH; n = 3) and myelodysplastic syndrome (MDS; n = 2). A compound heterozygous case of AA showed clonal evolution. Our results suggest that some of the inherited CTC 1 variants may represent predisposition factors for acquired bone marrow failure.