The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita.
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.
Vulliamy
T
T
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.
Marrone
A
A
Goldman
F
F
Dearlove
A
A
Bessler
M
M
Mason
P J
PJ
Dokal
I
I
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
D012313:RNA; D019098:Telomerase