The RNA Component of Telomerase Is Mutated in Autosomal Dominant Dyskeratosis Congenita

Nature. 2001 Sep 27;413(6854):432-5. doi: 10.1038/35096585.

Abstract

Dyskeratosis congenita is a progressive bone-marrow failure syndrome that is characterized by abnormal skin pigmentation, leukoplakia and nail dystrophy. X-linked, autosomal recessive and autosomal dominant inheritance have been found in different pedigrees. The X-linked form of the disease is due to mutations in the gene DKC1 in band 2, sub-band 8 of the long arm of the X chromosome (ref. 3). The affected protein, dyskerin, is a nucleolar protein that is found associated with the H/ACA class of small nucleolar RNAs and is involved in pseudo-uridylation of specific residues of ribosomal RNA. Dyskerin is also associated with telomerase RNA (hTR), which contains a H/ACA consensus sequence. Here we map the gene responsible for dyskeratosis congenita in a large pedigree with autosomal dominant inheritance. Affected members of this family have an 821-base-pair deletion on chromosome 3q that removes the 3' 74 bases of hTR. Mutations in hTR were found in two other families with autosomal dominant dyskeratosis congenita.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3*
  • DNA Mutational Analysis
  • Dyskeratosis Congenita / genetics*
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Point Mutation
  • RNA / genetics*
  • Telomerase / genetics*
  • Telomere

Substances

  • RNA
  • Telomerase