Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita

Erin M. Parry, Jonathan K. Alder, Stella S. Lee, John A. Phillips, James E. Loyd, Priya Duggal, Mary Armanios

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Dyskeratosis congenita (DC) is a premature ageing syndrome characterised by short telomeres. An X-linked form of DC is caused by mutations in DKC1 which encodes dyskerin, a telomerase component that is essential for telomerase RNA stability. However, mutations in DKC1 are identifiable in only half of X-linked DC families. A four generation family with pulmonary fibrosis and features of DC was identified. Affected males showed the classic mucocutaneous features of DC and died prematurely from pulmonary fibrosis. Although there were no coding sequence or splicing variants, genome wide linkage analysis of 16 individuals across four generations identified significant linkage at the DKC1 locus, and was accompanied by reduced dyskerin protein levels in affected males. Decreased dyskerin levels were associated with compromised telomerase RNA levels and very short telomeres. These data identify decreased dyskerin levels as a novel mechanism of DC, and indicate that intact dyskerin levels, in the absence of coding mutations, are critical for telomerase RNA stability and for in vivo telomere maintenance.

Original languageEnglish (US)
Pages (from-to)327-333
Number of pages7
JournalJournal of medical genetics
Issue number5
StatePublished - May 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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