Dyskeratosis congenita (DC) is an inherited disorder characterized by skin 
pigmentation, nail dystrophy and mucosal leucoplakia. In 1995 a Dyskeratosis 
Congenita Registry was established at the Hammersmith Hospital. In the 46 
families recruited, 76/83 patients were male, suggesting that the major form of 
DC is X-linked. As well as a variety of noncutaneous abnormalities, the majority 
(93%) of patients had bone marrow (BM) failure and this was the principal cause 
(71%) of early mortality. In addition to BM hypoplasia, some patients also 
developed myelodysplasia and acute myelod leukaemia. Pulmonary abnormalities 
were present in 19% of patients. In affected females the phenotype was less 
severe. Some female carriers of X-linked DC had clinical features. Carriers of 
X-linked DC showed skewed X-chromosome inactivation patterns (XCIPs), suggesting 
that cells expressing the normal DC allele have a growth/survival advantage over 
cells that express the mutant allele. Linkage analysis in multiplex families 
confirmed that the DKC1 gene, responsible for the X-linked form of DC, is 
located within Xq28 and facilitated its positional cloning. The high incidence 
of BM failure in association with a wide range of somatic abnormalities together 
with the ubiquitous expression of DKC1 suggest that, as well as having a 
critical role in normal haemopoiesis, this gene has a key role in normal cell 
biology.