[Dyskeratosis congenita, a disease caused by defective telomere maintenance]

Med Sci (Paris). 2008 Apr;24(4):390-8. doi: 10.1051/medsci/2008244390.
[Article in French]

Abstract

Dyskeratosis congenita (DC), also called Zinsser-Cole-Engman syndrome, is a rare, often fatal, inherited disease described for the first time at the dermatological level by Zinsser in 1906. It is a very polymorphous disease at the clinical level, with several modes of inheritance. Several clinical symptoms of the disease can appear after a latency period. These features render DC particularly difficult to diagnose. Mutations of several genes can cause DC, four of them having been identified so far. However, for a majority of patients, the affected gene has not been found. Remarkably, all identified genes (DKC1, hTERC, hTERT, and NOP10) encode components of telomerase, all required for telomere length maintenance. DC is thus a unique clinical model for the study of the roles of telomerase and telomeres. Moreover, proteins encoded by the DKC1 and NOP10 genes are also components of so-called box H/ACA RNPs required for ribosome synthesis and pre-mRNA processing. Alterations of these processes could contribute to the symptoms of DC patients carrying mutations in DKC1 or NOP10.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Dyskeratosis Congenita / diagnosis
  • Dyskeratosis Congenita / genetics*
  • Dyskeratosis Congenita / physiopathology
  • Humans
  • Models, Genetic
  • Phenotype
  • Pseudouridine / metabolism
  • RNA / genetics
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomere / genetics*
  • Uridine / metabolism

Substances

  • Pseudouridine
  • RNA
  • Telomerase
  • Uridine