One novel and two recurrent missense DKC1 mutations in patients with dyskeratosis congenita (DKC).

X-linked dyskeratosis congenita (DKC) is a progressive multisystem disorder most severely affecting tissues with a high cellular turnover such as skin, mucous membranes, and blood. Most patients die of bone marrow failure, although the chances of succumbing to various types of cancer and pulmonary disease are also high. DKC is caused predominantly by missense mutations in the DKC1 gene linked to Xq28. Some of the clinical features are reminiscent of premature ageing and this agrees with recent indications that DKC could be a telomere maintenance disorder. There is considerable variability in the type, severity, and age at onset of the various anomalies. Recognition of this has increased with the finding that patients with Hoyeraal-Hreidarsson syndrome (HHS) who exhibit severe neurological problems in addition to early-onset pancytopenia, also bear mutations in the DKC1 gene. For these reasons, and compounded by the range of mutations, phenotype-genotype correlations and accurate assessments of prognosis have not been possible. To complement the present data, we here report on three new cases of DKC and their mutations. One is a novel mutation in the exon 3 (K43E). The other two represent a frequently recurring mutation in exon 11 (A353V) and a less frequently recurring mutation in the exon 3 (T49M).