Comment in:

Nature. 2001 Sep 27;413(6854):370-1, 373.

The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita.

Department of Haematology, Division of Investigative Science, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Hammersmith Hospital, Ducane Road, London W12 ONN, UK.

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.

PMID: 11574891 [PubMed - indexed for MEDLINE]