title: The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita.
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.
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Vulliamy
authors.forename: A
authors.initials: A
authors.lastname: Marrone
authors.forename: F
authors.initials: F
authors.lastname: Goldman
authors.forename: A
authors.initials: A
authors.lastname: Dearlove
authors.forename: M
authors.initials: M
authors.lastname: Bessler
authors.forename: P J
authors.initials: PJ
authors.lastname: Mason
authors.forename: I
authors.initials: I
authors.lastname: Dokal
mesh_terms: D002460:Cell Line; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D004252:DNA Mutational Analysis; D019871:Dyskeratosis Congenita / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D016615:Telomere
chemical_list: D012313:RNA; D019098:Telomerase