Dyskeratosis Congenita (DC) Registry: identification of new features of DC

Br J Haematol. 1998 Dec;103(4):990-6. doi: 10.1046/j.1365-2141.1998.01103.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cause of Death
  • Child
  • Child, Preschool
  • Dyskeratosis Congenita / genetics*
  • Female
  • Genetic Linkage
  • Hematologic Diseases / genetics
  • Heterozygote
  • Humans
  • Infant
  • Lung Diseases / genetics
  • Male
  • Pedigree
  • Phenotype
  • Registries
  • Sex Factors
  • X Chromosome / genetics