Telomerase RNA deficiency in peripheral blood mononuclear cells in X-linked dyskeratosis congenita

Hum Genet. 2004 Oct;115(5):448-55. doi: 10.1007/s00439-004-1178-7. Epub 2004 Sep 3.


Compromised renewal and eventual failure of the hematopoietic system in dyskeratosis congenita (DC) have been proposed to arise from a deficiency in telomerase function. Previously, cultured cell lines from patients with X-linked DC were shown to accumulate less telomerase RNA than cell lines from unaffected family members. Here, we report that telomerase RNA deficiency is also present in the circulating lymphocytes of DC patients. We have compared the accumulation levels of telomerase RNA and a panel of other small RNAs in peripheral blood mononuclear cells from an X-linked DC patient and an unaffected maternal carrier and similarly analyzed cultured lymphoblasts from an X-linked DC patient and maternal carrier in a second family. The DC-patient lymphoid cells show a specific defect in telomerase RNA accumulation with or without cell culture. Our findings support the clinical significance of telomerase deficiency and encourage the use of telomerase activation as a disease therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Northern
  • Cell Cycle Proteins / blood
  • Cell Cycle Proteins / genetics*
  • Cell Line, Transformed
  • Dyskeratosis Congenita / blood
  • Dyskeratosis Congenita / genetics*
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Nuclear Proteins / blood
  • Nuclear Proteins / genetics*
  • RNA / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase / blood
  • Telomerase / deficiency*


  • Cell Cycle Proteins
  • DKC1 protein, human
  • Nuclear Proteins
  • telomerase RNA
  • RNA
  • Telomerase