The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
TINF2, a Component of the Shelterin Telomere Protection Complex, Is Mutated in Dyskeratosis Congenita
Open accessAbstract
Patients with dyskeratosis congenita (DC), a heterogeneous inherited bone marrow failure syndrome, have abnormalities in telomere biology, including very short telomeres and germline mutations in DKC1, TERC, TERT, or NOP10, but approximately 60% of DC patients lack an identifiable mutation. With the very short telomere phenotype and a highly penetrant, rare disease model, a linkage scan was performed on a family with autosomal-dominant DC and no mutations in DKCI, TERC, or TERT. Evidence favoring linkage was found at 2p24 and 14q11.2, and this led to the identification of TINF2 (14q11.2) mutations, K280E, in the proband and her five affected relatives and TINF2 R282H in three additional unrelated DC probands, including one with Revesz syndrome; a fifth DC proband had a R282S mutation. TINF2 mutations were not present in unaffected relatives, DC probands with mutations in DKC1, TERC, or TERT or 298 control subjects. We demonstrate that a fifth gene, TINF2, is mutated in classical DC and, for the first time, in Revesz syndrome. This represents the first shelterin complex mutation linked to human disease and confirms the role of very short telomeres as a diagnostic test for DC.
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“Shelterin mutations have been found in some cases of aplastic anemia and dyskeratosis congenita (Savage et al., 2008; Walne et al., 2008; Zhong et al., 2011).”
From The Hallmarks of Aging (2013) · cites this paper as Savage et al., 2008
In the citing paper
“Autosomal dominant forms are caused by mutations in TERT, TERC or the telomere binding protein TRF1-interacting nuclear factor 2 (156-159).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [156]
In the citing paper
“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 [62]
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Metadata
- Authors
- Savage, S. A., Giri, N., Baerlocher, G. M., Orr, N., Lansdorp, P. M., & Alter, B. P.
- Affiliations
- National Institutes of Health (US)
- University Hospital of Bern (CH)
- National Cancer Institute (US)
- Corresponding author
- Savage, Sharon A.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 82
- Issue
- 2
- Pages
- 501-509
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2427222
- OpenAlex
- W2033942199
- Cited by
- 414
- References
- 46
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 16 · 2023: 15 · 2022: 15 · 2021: 16 · 2020: 17 · 2019: 17 · 2018: 29 · 2017: 17 · 2016: 17 · 2015: 21 · 2014: 27 · 2013: 29 · 2012: 25
- FWCI
- 28.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (N02 CP011019)
- National Institute of Allergy and Infectious Diseases (AI 29524, R21AI029524, R01AI029524)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- TIN2, dyskeratosis congenita, shelterin complex, telomere protection, bone marrow failure, autosomal dominant inheritance, germline mutations, telomere biology
- MeSH terms
- Adolescent, Adult, Base Sequence, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Human, Pair 14, Humans, Molecular Sequence Data, Mutation, Pedigree, Telomere, Sequence Analysis, DNA, Dyskeratosis Congenita, Telomere-Binding Proteins
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