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Cited by 960Telomeres, Telomerase, and SenescenceBlood disorders and treatmentsNuclear Structure and Function

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

Vulliamy, Tom, Marrone, Anna, Goldman, Frederick, Dearlove, Andrew, Bessler, Monica, Mason, Philip J., Dokal, Inderjeet·2001·Nature
DOI 10.1038/35096585
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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.

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  • Because losing function of a single TERT or TR allele is enough to impair telomere maintenance, these mutations follow autosomal-dominant inheritance.

    “They manifest in an autosomal-dominant inheritance pattern because complete or partial loss-of-function of one allele is sufficient to perturb telomere maintenance38,39,41.”

    From The telomere syndromes (2012) · cites this paper as [38]

  • Eight genes have been found mutated in dyskeratosis congenita, and every one encodes a telomerase or telomere protein component.

    “Eight mutant genes have been identified in dyskeratosis congenita9,38,39,60–64, and all of them encode telomerase or telomere protein components (summarized in Table 1).”

    From The telomere syndromes (2012) · cites this paper as [38]

  • Dyskeratosis congenita features short telomeres as a defining characteristic.

    “Dyskeratosis congenita is characterized by the short telomere defect11,38,55.”

    From The telomere syndromes (2012) · cites this paper as [38]

  • Multiple different mutations in TERC have been described for patients with DKC.

    “Multiple different mutations in TERC have been described for patients with DKC (10).”

    From Adult-onset pulmonary fibrosis caused by mutations in telomerase (2007) · cites this paper as [10]

  • Individuals with TERT or TERC mutations have none of the physical manifestations of DKC and were all ascertained by the lung fibrosis phenotype, distinguishing them from previously described patients with mutations in these genes.

    “The individuals with TERT or TERC mutations have none of the physical manifestations of DKC and were all ascertained by the lung fibrosis phenotype, distinguishing them from previously described patients with mutations in these genes (6, 9, 10, 17).”

    From Adult-onset pulmonary fibrosis caused by mutations in telomerase (2007) · cites this paper as [10]

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Authors
Vulliamy, T., Marrone, A., Goldman, F., Dearlove, A., Bessler, M., Mason, P. J., & Dokal, I.
Affiliations
  • Hammersmith Hospital (GB)
  • University of Iowa Hospitals and Clinics (US)
  • Washington University in St. Louis (US)
Corresponding author
Mason, Philip J.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2001-09-27
Volume
413
Issue
6854
Pages
432-435
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/35096585
OpenAlex
W2044758458
Cited by
960
References
30
Citations by year
2026: 7 · 2025: 13 · 2024: 14 · 2023: 18 · 2022: 20 · 2021: 19 · 2020: 31 · 2019: 18 · 2018: 29 · 2017: 19 · 2016: 37 · 2015: 33 · 2014: 43 · 2013: 32 · 2012: 40
FWCI
35.53
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
dyskeratosis congenita, telomerase RNA, hTR, autosomal dominant inheritance, bone marrow failure, dyskerin, telomerase, gene mapping
MeSH terms
Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 3, DNA Mutational Analysis, Female, Genes, Dominant, Humans, Genetic Linkage, Male, Mutation, Pedigree, RNA, Telomere, Point Mutation, Telomerase, Dyskeratosis Congenita

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