title: Dyskeratosis Congenita (DC) Registry: identification of new features of DC.
abstract: 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.
authors.affiliation: Department of Haematology, Imperial College School of Medicine, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Knight
authors.forename: T
authors.initials: T
authors.lastname: Vulliamy
authors.forename: A
authors.initials: A
authors.lastname: Copplestone
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.forename: P
authors.initials: P
authors.lastname: Mason
authors.forename: I
authors.initials: I
authors.lastname: Dokal
mesh_terms: D000293:Adolescent; D000328:Adult; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D019871:Dyskeratosis Congenita / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006402:Hematologic Diseases / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000235:genetics; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012042:Registries; D012737:Sex Factors; D014960:X Chromosome / Q000235:genetics