RGD Reference Report - X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. - Rat Genome Database

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X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene.

Authors: Knight, SW  Heiss, NS  Vulliamy, TJ  Greschner, S  Stavrides, G  Pai, GS  Lestringant, G  Varma, N  Mason, PJ  Dokal, I  Poustka, A 
Citation: Knight SW, etal., Am J Hum Genet. 1999 Jul;65(1):50-8.
RGD ID: 10755414
Pubmed: PMID:10364516   (View Abstract at PubMed)
PMCID: PMC1378074   (View Article at PubMed Central)
DOI: DOI:10.1086/302446   (Journal Full-text)

Dyskeratosis congenita is a rare inherited bone marrow-failure syndrome characterized by abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. More than 80% of patients develop bone-marrow failure, and this is the major cause of premature death. The X-linked form of the disease (MIM 305000) has been shown to be caused by mutations in the DKC1 gene. The gene encodes a 514-amino-acid protein, dyskerin, that is homologous to Saccharomyces cerevisiae Cbf5p and rat Nap57 proteins. By analogy to the homologues in other species, dyskerin is predicted to be a nucleolar protein with a role in both the biogenesis of ribosomes and, in particular, the pseudouridylation of rRNA precursors. We have determined the genomic structure of the DKC1 gene; it consists of 15 exons spanning a region of 15 kb. This has enabled us to screen for mutations in the genomic DNA, by using SSCP analysis. Mutations were detected in 21 of 37 additional families with dyskeratosis congenita that were analyzed. These mutations consisted of 11 different single-nucleotide substitutions, which resulted in 10 missense mutations and 1 putative splicing mutation within an intron. The missense change A353V was observed in 10 different families and was shown to be a recurring de novo event. Two polymorphisms were also detected, one of which resulted in the insertion of an additional lysine in the carboxy-terminal polylysine domain. It is apparent that X-linked dyskeratosis congenita is predominantly caused by missense mutations; the precise effect on the function of dyskerin remains to be determined.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dyskeratosis congenita  IAGP 10755414DNA:missense mutations more ...RGD 
dyskeratosis congenita  ISODKC1 (Homo sapiens)10755414; 10755414DNA:missense mutations more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dkc1  (dyskerin pseudouridine synthase 1)

Genes (Mus musculus)
Dkc1  (dyskeratosis congenita 1, dyskerin)

Genes (Homo sapiens)
DKC1  (dyskerin pseudouridine synthase 1)


Additional Information