The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index; none of the 31 sources its claims cite is checked for support yet.
Adult-onset pulmonary fibrosis caused by mutations in telomerase
Open accessAbstract
Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung disease of unknown etiology. Some individuals with IPF have a familial disorder that segregates as a dominant trait with incomplete penetrance. Here we used linkage to map the disease gene in two families to chromosome 5. Sequencing a candidate gene within the interval, TERT , revealed a missense mutation and a frameshift mutation that cosegregated with pulmonary disease in the two families. TERT encodes telomerase reverse transcriptase, which together with the RNA component of telomerase ( TERC ), is required to maintain telomere integrity. Sequencing the probands of 44 additional unrelated families and 44 sporadic cases of interstitial lung disease revealed five other mutations in TERT . A heterozygous mutation in TERC also was found in one family. Heterozygous carriers of all of the mutations in TERT or TERC had shorter telomeres than age-matched family members without the mutations. Thus, mutations in TERT or TERC that result in telomere shortening over time confer a dramatic increase in susceptibility to adult-onset IPF.
Overview
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Written from the paper’s full text.
TL;DR
Mutations in *TERT* or *TERC* that cause telomere shortening confer susceptibility to adult-onset idiopathic pulmonary fibrosis (IPF). The study links telomerase dysfunction to familial and sporadic IPF, with incomplete penetrance and possible smoking exacerbation.
Key findings
- Linkage in two large families mapped disease to chromosome 5p15 with a maximal LOD score of 2.8; sequencing the candidate gene *TERT* found a missense mutation (R865H) and a frameshift mutation (V747fsX766) that cosegregated with pulmonary disease.
- In 44 additional unrelated familial interstitial lung disease probands and 44 sporadic cases, five other *TERT* mutations were found (total: two frameshift deletions and five missense mutations), plus one heterozygous *TERC* mutation (r.37a>g); none of the seven *TERT* mutations were found in 94 ethnically matched controls, 200 patients with aplastic anemia, or a multiethnic panel of 528 controls.
- Heterozygous carriers of *TERT* or *TERC* mutations had shorter telomeres than age-matched family members without the mutations; in vitro TRAP assays showed frameshift mutants had little detectable telomerase activity, missense and *TERC* mutants ranged from zero to 100% of wild-type activity, and mixing V747fs with wild-type *TERT* suggested haploinsufficiency.
- Among mutation carriers, smokers died at an average age of 58 years (n = 13) versus 68 years for nonsmokers (n = 7); all affected individuals developed pulmonary fibrosis in adulthood with no history of pediatric lung disease.
Methods
- Clinical sample: 46 families with two or more cases of idiopathic interstitial lung disease (34 of 46 families had individuals with IPF) and 44 sporadic interstitial lung disease cases (31 with IPF); genomic DNA was isolated from leukocytes, and for four individuals from formalin-fixed paraffin-embedded archival samples.
- Linkage analysis: whole-genome SNP genotyping with the Illumina Linkage IVb panel of >6,000 polymorphic SNPs; MERLIN was used for multipoint model-free and model-based linkage analysis, with the highest peak on chromosome 5p15.
- Mutation and functional analysis: *TERT* exons and splice sites and 451 bp encoding *TERC* were sequenced; telomerase activity was measured by the TRAP assay using in vitro coexpressed recombinant protein and RNA; telomere length was assessed by terminal restriction fragment (TRF) Southern blot analysis of leukocyte DNA.
Limitations
- The paper does not include a formal limitations section; it states that pulmonary fibrosis appears to be a human-specific manifestation of telomerase deficiency and that it is not yet reported whether aged telomerase-deficient mice develop similar lung pathology.
- The paper notes incomplete penetrance: some family members who inherited a *TERT* mutation had no evidence of pulmonary disease, and environmental influences such as cigarette smoking may affect the phenotype.
- Evident from the text: linkage mapping relied on two families, mutation screening focused on the candidate genes *TERT* and *TERC*, and in vitro TRAP activity did not always track telomere shortening because some mutations caused telomere shortening without a detectable decrease in telomerase activity.
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24 Own result · 21 Not checked yet · 8 Own interpretation · 4 Own method · 1 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sequencing a candidate gene within the interval, TERT, revealed a missense mutation and a frameshift mutation that cosegregated with pulmonary disease in the two families.”
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In the paper
“A heterozygous mutation in TERC also was found in one family.”
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In the paper
“Here we used linkage to map the disease gene in two families to chromosome 5.”
- Also stated in: § Results · plain
“Both families displayed linkage to chromosome 5p15 with a maximal logarithm of odds (LOD) score of 2.8.”
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sequencing the probands of 44 additional unrelated families and 44 sporadic cases of interstitial lung disease revealed five other mutations in TERT.”
plainn = 44- Asserted: passes — The authors put it forward as true.
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In the paper
“Heterozygous carriers of all of the mutations in TERT or TERC had shorter telomeres than age-matched family members without the mutations.”
- Also stated in: § Results · plain
“When compared with normal family members of similar age, the mean telomere length was significantly shorter for those individuals who were heterozygous for a mutation in TERT or TERC (Fig. 5 A and B).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, a total of two frameshift deletions and five missense mutations in TERT were identified in patients with pulmonary fibrosis (Fig. 3).”
plainn = 44- Asserted: passes — The authors put it forward as true.
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In the paper
“When telomere lengths were analyzed within families, the family members with clinical disease tended to have shorter TRFs than the asymptomatic carriers.”
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In the paper
“Mixing different amounts of the V747fs TERT construct with the wild-type TERT construct did not affect the activity of the wild-type protein, suggesting a mechanism of haploinsufficiency (Fig. 4D).”
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In the paper
“The proband of family F11 was heterozygous for a transition mutation (CGT → CAT) in codon 865 that is predicted to change a highly conserved arginine to a histidine.”
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In the paper
“The five missense mutations in TERT (Fig. 4 B and C) and the mutation in TERC (Fig. 4 A and C) produced levels of telomerase activity that ranged from zero to 100% of wild-type activity.”
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“Four additional sequence variations, including three missense mutations and one 177-bp deletion, were found (Fig. 3).”
plainn = 44- Asserted: passes — The authors put it forward as true.
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In the paper
“None of the seven mutations were found in 94 locally collected, ethnically matched individuals, nor were they detected in 200 patients with aplastic anemia or a multiethnic panel of 528 individuals sequenced as controls (9).”
What the sources say
- Not checked yetcites [9] Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. N Engl J Med. 2005;352:1413–1424. doi: 10.1056/NEJMoa042980. [DOI] [PubMed] [Google Scholar] source
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In the paper
“All developed pulmonary fibrosis during their adult years with no history of pediatric lung disease, in contrast with kindreds associated with surfactant protein C mutations (18, 19).”
What the sources say
- Not checked yetcites [18] Thomas AQ, Lane K, Phillips J, III, Prince M, Markin C, Speer M, Schwartz DA, Gaddipati R, Marney A, Johnson J, et al. Am J Respir Crit Care Med. 2002;165:1322–1328. doi: 10.1164/rccm.200112-123OC. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [19] Nogee LM, Dunbar AE, III, Wert SE, Askin F, Hamvas A, Whitsett JA. N Engl J Med. 2001;344:573–579. doi: 10.1056/NEJM200102223440805. [DOI] [PubMed] [Google Scholar] source
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In the paper
“None had aplastic anemia but several exhibited a mild to moderate anemia and one individual developed neutropenia after lung transplantation.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“One additional missense mutation was identified involving the same arginine at codon 865 found to be mutated in family F11.”
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Another individual with a TERT mutation in this family had very short TRFs but did not have IPF. This individual had cirrhosis of unknown etiology.”
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“The proband of family F31 was heterozygous for a deletion of thymidine at position 2240 in the cDNA, which creates a frameshift in the reading frame and is predicted to result in a truncated protein missing half of the reverse-transcriptase domain and the entire C-terminal region.”
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In the paper
“As expected, the mutation (V747fs, Fig. 4 A and C) missing half the reverse transcriptase domain and the mutation (E1116fs; Fig. 4C) missing the C-terminal E-IV domain had very little detectable telomerase activity.”
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In the paper
“This change was not detected in 94 ethnically matched controls but was identified previously in a person with severe aplastic anemia who was a compound heterozygote for variants in TERC (12).”
What the sources say
- Not checked yetcites [12] Ly H, Schertzer M, Jastaniah W, Davis J, Yong SL, Ouyang Q, Blackburn EH, Parslow TG, Lansdorp PM. Blood. 2005;106:1246–1252. doi: 10.1182/blood-2005-01-0247. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper
“A number of individuals had evidence of axial osteoporosis; in many cases, this diagnosis preceded or was determined in the absence of lung disease.”
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In the paper
“For both families, some family members with TERT mutations exhibited other clinical features of DKC (7), such as osteoporosis/osteopenia, anemia and cancer (Table 1), but none of the affected individuals had the mucocutaneous lesions typical of DKC.”
What the sources say
- Not checked yetcites [7] Dokal I. Br J Haematol. 2000;110:768–779. doi: 10.1046/j.1365-2141.2000.02109.x. [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
What the sources say
- Not checked yetcites [6] Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Proc Natl Acad Sci USA. 2005;102:15960–15964. doi: 10.1073/pnas.0508124102. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [9] Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. N Engl J Med. 2005;352:1413–1424. doi: 10.1056/NEJMoa042980. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [10] Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I. Nature. 2001;413:432–435. doi: 10.1038/35096585. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [17] Fogarty PF, Yamaguchi H, Wiestner A, Baerlocher GM, Sloand E, Zeng WS, Read EJ, Lansdorp PM, Young NS. Lancet. 2003;362:1628–1630. doi: 10.1016/S0140-6736(03)14797-6. [DOI] [PubMed] [Google Scholar] source
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In the paper
“One proband of a Caucasian family (F61) was heterozygous for an adenosine and guanine at position 37.”
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung disease of unknown etiology.”
- Also stated in: § Abstract · plain
“IPF is distinguished from the other interstitial lung diseases by its unknown etiology, by characteristic abnormalities on pulmonary function tests and radiographs, and by biopsy findings, which include evidence of injury occurring over time with foci of replicating fibroblasts at the interface between normal and scarred lung tissue (3).”
What the sources say
- Not checked yetcites [3] American Thoracic Society/European Respiratory Society. Am J Respir Crit Care Med. 2002;165:277–304. doi: 10.1164/ajrccm.165.2.ats01. [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Among the genes we evaluated was TERT, which was considered a candidate because a mutation in this gene was recently reported to cause autosomal dominant dyskeratosis congenita (DKC), a disorder in which 20% of affected individuals develop pulmonary fibrosis (6, 7).”
What the sources say
- Not checked yetcites [6] Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Proc Natl Acad Sci USA. 2005;102:15960–15964. doi: 10.1073/pnas.0508124102. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [7] Dokal I. Br J Haematol. 2000;110:768–779. doi: 10.1046/j.1365-2141.2000.02109.x. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The clinical presentation of familial IPF is indistinguishable from sporadic IPF except that the age of onset tends to be earlier (55 years vs. 67 years) (4, 5).”
What the sources say
- Not checked yetcites [4] Marshall RP, Puddicombe A, Cookson WO, Laurent GJ. Thorax. 2000;55:143–146. doi: 10.1136/thorax.55.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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In the paper
“All sequences were determined in both directions, the mutations were confirmed by three separate PCR amplification products, and both genes were sequenced in their entirety for all subjects.”
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In the paper
“Telomere length is also influenced by oxidative damage (24) that, in part, may explain why lung disease is the predominant phenotype and why smoking may exacerbate this disease.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The pathologic features of IPF suggest that the lung injury is focal, affecting scattered portions of the lung parenchyma and recurring over many years (21).”
What the sources say
- Not checked yetcites [21] Katzenstein AL, Myers JL. Am J Respir Crit Care Med. 1998;157:1301–1315. doi: 10.1164/ajrccm.157.4.9707039. [DOI] [PubMed] [Google Scholar] source
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In the paper
“Repeat experiments showed the same relative trend of TRAP activities.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Multiple different mutations in TERC have been described for patients with DKC (10).”
What the sources say
- Not checked yetcites [10] Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I. Nature. 2001;413:432–435. doi: 10.1038/35096585. [DOI] [PubMed] [Google Scholar] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pulmonary fibrosis appears to be a human-specific manifestation of telomerase deficiency.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Call rates varied from 99.7–100% for Autopure-purified DNA and between 72–98% for whole-genome-amplified DNA extracted from archival samples.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Telomerase may be a marker for identifying resident stem cells that promote regeneration and prevent premature aging of the lung.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Smoking causes telomere shortening in a dose-dependent manner (22) and is associated with familial interstitial pneumonia (23).”
What the sources say
- Not checked yetcites [22] Morla M, Busquets X, Pons J, Sauleda J, MacNee W, Agusti AG. Eur Respir J. 2006;27:525–528. doi: 10.1183/09031936.06.00087005. [DOI] [PubMed] [Google Scholar] source
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plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, a recent trial with high doses of the antioxidant acetylcysteine appeared to attenuate the progression of IPF (25).”
What the sources say
- Not checked yetcites [25] Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W, Thomeer M, Wallaert B, Laurent F, et al. N Engl J Med. 2005;353:2229–2242. doi: 10.1056/NEJMoa042976. [DOI] [PubMed] [Google Scholar] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This report provides previously undescribed molecular insight into the pathogenesis of IPF and expands the scope of diseases caused by mutations in telomerase.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Telomere length is influenced by many different factors, including age (13, 14) and the number of generations the mutation is transmitted (6, 15).”
What the sources say
- Not checked yetcites [13] Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC. Nature. 1990;346:866–868. doi: 10.1038/346866a0. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [14] Harley CB, Futcher AB, Greider CW. Nature. 1990;345:458–460. doi: 10.1038/345458a0. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [6] Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Proc Natl Acad Sci USA. 2005;102:15960–15964. doi: 10.1073/pnas.0508124102. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [15] Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, Dokal I. Nat Genet. 2004;36:447–449. doi: 10.1038/ng1346. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study was approved by the University of Texas Southwestern Institutional Review Board. Written informed consent was obtained from all participants.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such a pattern of injury could explain why the pulmonary phenotype is incompletely penetrant and may be influenced not only by the nature of the mutations but also by environmental influences, such as cigarette smoking.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
TERT encodes telomerase reverse transcriptase, which together with TERC is required to maintain telomere integrity.
“TERT encodes telomerase reverse transcriptase, which together with the RNA component of telomerase (TERC), is required to maintain telomere integrity.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The fact that AAV9-TERT treatment of old mice efficiently reactivated telomerase in the lungs offers a therapeutic opportunity for some cases of human pulmonary fibrosis associated with presence of short telomeres owing to telomerase mutations (Armanios et al, 2007; Tsakiri et al, 2007).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Tsakiri et al, 2007
In the citing paper
“The frequency of these mutations is highest in individuals with the progressive disorder IPF, which accounts for 8–15% of familial and 1–3% of sporadic cases54,56,68,69.”
From The telomere syndromes (2012) · cites this paper as [68]
In the citing paper
“By contrast, telomere shortening is accelerated in several human premature ageing syndromes, and patients with dyskeratosis congenita and aplastic anaemia show decreased telomerase activity and shortened telomeres owing to mutations in the TERC and TERT telomerase genes.”
From The common biology of cancer and ageing (2007) · cites this paper as [63]
In the citing paper
“patients who have inherited or acquired genetic defects that limit telomere maintenance seem to be at substantially increased risk of a range of conditions including aplastic anaemia 61 , idiopathic pulmonary fibrosis 62, 63 and the rarer dyskeratosis congenita syndrome”
From The common biology of cancer and ageing (2007) · cites this paper as [63]
Citations
Cites
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
(2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.2.ats01 · Cited by 4,196
Merlin—rapid analysis of dense genetic maps using sparse gene flow trees
Abecasis, G. R., Cherny, S. S., Cookson, W., & Cardon, L. R. (2001) · Nature Genetics · doi:10.1038/ng786 · Cited by 3,323
Oxidative stress shortens telomeres
von Zglinicki, T. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02110-2 · Cited by 2,524
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion
den Dunnen, J. T., & Antonarakis, S. E. (2000) · Human Mutation · doi:10.1002/(sici)1098-1004(200001)15:1 · Cited by 1,757
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349
Incidence and Prevalence of Idiopathic Pulmonary Fibrosis
Raghu, G., Weycker, D., Edelsberg, J., Bradford, W. Z., & Oster, G. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200602-163oc · Cited by 1,310
Self-citationIdiopathic Pulmonary Fibrosis: Clinical Relevance of Pathologic Classification
KATZENSTEIN, A.-L. A., & MYERS, J. L. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.4.9707039 · Cited by 1,261
Cited by
Sorted by citations
Raghu, G., Collard, H. R., Egan, J. J., Martinez, F. J., Behr, J., Brown, K. K., Colby, T. V., Cordier, J.-F., Flaherty, K. R., Lasky, J. A., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2009-040gl · Cited by 7,186
Self-citationMechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541
“Telomere shortening has been hypothesized to be an important contributor to the development of adult-onset and familial forms of pulmonary fibrosis 128,129 .”
King, T. E., Pardo, A., & Selman, M. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60052-4 · Cited by 2,194
Richeldi, L., Collard, H. R., & Jones, M. G. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30866-8 · Cited by 2,020
Lederer, D. J., & Martinez, F. J. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1705751 · Cited by 2,056
Metadata
- Authors
- Tsakiri, K. D., Cronkhite, J. T., Kuan, P. J., Xing, C., Raghu, G., Weissler, J. C., Rosenblatt, R. L., Shay, J. W., & Garcia, C. K.
- Affiliations
- *McDermott Center for Human Growth and Development,
- University of Washington Medical Center (US)
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine,
- The University of Texas Southwestern Medical Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-05
- Volume
- 104
- Issue
- 18
- Pages
- 7552-7557
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1855917
- OpenAlex
- W2115176808
- Cited by
- 894
- References
- 35
- Citations by year
- 2026: 24 · 2025: 35 · 2024: 30 · 2023: 35 · 2022: 49 · 2021: 62 · 2020: 54 · 2019: 43 · 2018: 45 · 2017: 41 · 2016: 40 · 2015: 61 · 2014: 50 · 2013: 50 · 2012: 53
- FWCI
- 47.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P50CA75907, P50CA070907)
- National Center for Research Resources (K23RR020632)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- idiopathic pulmonary fibrosis, telomerase reverse transcriptase, TERC, telomerase RNA, telomere shortening, genetic linkage, familial pulmonary fibrosis, missense mutations, frameshift mutation, interstitial lung disease, genetic susceptibility, chromosome 5
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Animals, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Pulmonary Fibrosis, Sequence Alignment, Telomere, Age of Onset, Telomerase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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