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.
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- 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
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plaindirect- Asserted: passes — The authors put it forward as true.
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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.
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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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
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“Telomere shortening has been hypothesized to be an important contributor to the development of adult-onset and familial forms of pulmonary fibrosis 128,129 .”
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“Recent studies have shown that mutations in the genes encoding telomerase components are also implicated in familial idiopathic pulmonary fibrosis (6, 209).”
BackgroundAcute Exacerbations of Idiopathic Pulmonary Fibrosis
Collard, H. R., Moore, B. B., Flaherty, K. R., Brown, K. K., Kaner, R. J., King, T. E., Lasky, J. A., Loyd, J. E., Noth, I., Olman, M. A., et al. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200703-463pp · Cited by 1,130
Self-citationThe common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988
Armanios, M., & Blackburn, E. H. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3246 · Cited by 982
Telomeres and telomerase: three decades of progress
Shay, J. W., & Wright, W. E. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0099-1 · Cited by 924
Self-citationPathogenesis of Idiopathic Pulmonary Fibrosis
Wolters, P. J., Collard, H. R., & Jones, K. D. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104706 · Cited by 888
“mutation and a frameshift V747fs mutation in the probands of the two kindreds (34).”
How stem cells age and why this makes us grow old
Sharpless, N. E., & DePinho, R. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2241 · Cited by 743
Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis
Fingerlin, T. E., Murphy, E., Zhang, W., Peljto, A. L., Brown, K. K., Steele, M. P., Loyd, J. E., Cosgrove, G. P., Lynch, D., Groshong, S., et al. (2013) · Nature Genetics · doi:10.1038/ng.2609 · Cited by 809
Self-citationShort telomeres are a risk factor for idiopathic pulmonary fibrosis
Alder, J. K., Chen, J. J.-L., Lancaster, L., Danoff, S., Su, S.-C., Cogan, J. D., Vulto, I., Xie, M., Qi, X., Tuder, R. M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804280105 · Cited by 805
“Mutations in telomerase components, hTERT and hTR, underlie inheritance of IPF in 8–15% of individuals who have a documented family history (5, 6).”
BackgroundCalado, R. T., & Young, N. S. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0903373 · Cited by 814
Telomere length, stem cells and aging
Blasco, M. A. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.38 · Cited by 747
“This further expands the number of human diseases characterized by regeneration defects that are associated with telomerase defect”
BackgroundIdiopathic pulmonary fibrosis: Disease mechanisms and drug development
Spagnolo, P., Kropski, J. A., Jones, M. G., Lee, J. S., Rossi, G., Karampitsakos, Τ., Maher, T. M., Tzouvelekis, A., & Ryerson, C. J. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107798 · Cited by 654
Pulmonary fibrosis: patterns and perpetrators
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“The most common mutations identified in familial pulmonary fibrosis are those in the genes encoding telomerase ( TERT and TERC ) (18, 19).”
Telomere Shortening in Familial and Sporadic Pulmonary Fibrosis
Cronkhite, J. T., Xing, C., Raghu, G., Chin, K. M., Torres, F., Rosenblatt, R. L., & Kim Garcia, C. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200804-550oc · Cited by 573
“In epidemiologic studies, IPF is diagnosed more commonly in males than females (1).”
BackgroundMethodResultInfluentialSelf-citationTargeting telomeres and telomerase
Cian, A. D., Lacroix, L., Douarre, C., Temime‐Smaali, N., Trentesaux, C., Riou, J., & Mergny, J. (2007) · Biochimie · doi:10.1016/j.biochi.2007.07.011 · Cited by 583
Pathophysiology and management of inherited bone marrow failure syndromes
Shimamura, A., & Alter, B. P. (2010) · Blood Reviews · doi:10.1016/j.blre.2010.03.002 · Cited by 570
“Unlike FA and DC, with chromosome breakage and telomere length serving as highly sensitive screening tests, the diagnosis of DBA is not so clear-cut; it is reviewed elsewhere.(50) Blood counts usually demonstrate macrocytic anemia with reticulocytopenia, often with increased and Hb F, as well as elevated red cell aden…”
BackgroundInfluentialBernardes de Jesus, B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201200245 · Cited by 548
“…with impaired telomerase activity (Armanios et al, 2007; Blasco TERT alone extends lifespan of adult/old mice , 1997; Flores et al, 2005; Garcia-Cao et al, 2006; Herrera et al, 1999; Mitchell et al, 1999; Schoeftner et al, 2009; Tsakiri et al, 2007; Vulliamy et al, 2001; Yamaguchi et al, 2005).”
Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins
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Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells
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“Reduced telomerase activity due to mutations in telomerase components in the human diseases dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis (Mitchell et al., 1999; Yamaguchi et al., 2005; Tsakiri et al., 2007; Armanios et al., 2007) further accelerates telomere shortening and leads to premat…”
BackgroundLandi, M. T., Chatterjee, N., Yu, K. F., Goldin, L. R., Goldstein, A. M., Rotunno, M., Mirabello, L. J., Jacobs, K. B., Wheeler, W., Yeager, M., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.05.003 · Cited by 498
Genetic Defects in Surfactant Protein A2 Are Associated with Pulmonary Fibrosis and Lung Cancer
Wang, Y., Kuan, P. J., Xing, C., Cronkhite, J. T., Torres, F., Rosenblatt, R. L., DiMaio, J. M., Kinch, L. N., Grishin, N. V., & Garcia, C. K. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.11.010 · Cited by 513
“Photographs were obtained as previously described.(4) Slides from a normal subject (K), a sporadic patient with IPF without any mutations in SFTPA2 (L), a patient with adenocarcinoma with BAC features and no SFTPA2 genomic mutations (N) and F27 family members IV:8 (M), IV:7 (O), and III:12 (P) were stained for immunoc…”
MethodSelf-citationLandi, M. T., Chatterjee, N., Yu, K. F., Goldin, L. R., Goldstein, A. M., Rotunno, M., Mirabello, L. J., Jacobs, K. B., Wheeler, W., Yeager, M., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.09.012 · Cited by 497
Alveolar Surfactant Homeostasis and the Pathogenesis of Pulmonary Disease
Whitsett, J. A., Wert, S. E., & Weaver, T. E. (2010) · Annual Review of Medicine · doi:10.1146/annurev.med.60.041807.123500 · Cited by 500
“Heterozygous mutations in genes encoding two essential components of telomerase, TERT (OMIM #187270) and telomerase RNA component (TERC, OMIM #602322), are also associated with pulmonary fibrosis (12, 13).”
InfluentialTelomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice
Tomás-Loba, A., Flores, I., Fernández-Marcos, P. J., Cayuela, M. L., Maraver, A., Tejera, A., Borrás, C., Matheu, A., Klatt, P., Flores, J. M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.09.034 · Cited by 484
“…anemia, and idiopathic pulmonary fibrosis, are linked to germline mutations in Tert and Terc genes, which result in decreased telomerase activity and accelerated telomere shortening (Mitchell et al., 1999; Vulliamy et al., 2001; Yamaguchi et al., 2005; Tsakiri et al., 2007; Armanios et al., 2007).”
BackgroundRothman, N., García‐Closas, M., Chatterjee, N., Malats, N., Wu, X., Figueroa, J. D., Real, F. X., Berg, D. V. D., Matullo, G., Baris, D., et al. (2010) · Nature Genetics · doi:10.1038/ng.687 · Cited by 471
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“These were also similar to the telomere length measurements of TERT and TERC mutation carriers22.”
MethodInfluentialSelf-citationTargeted Injury of Type II Alveolar Epithelial Cells Induces Pulmonary Fibrosis
Sisson, T. H., Mendez, M. P., Choi, K., Subbotina, N., Courey, A. J., Cunningham, A. K., Dave, A., Engelhardt, J. F., Liu, X., White, E. S., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200810-1615oc · Cited by 483
Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology
Vancheri, C., Failla, M., Crimi, N., & Raghu, G. (2010) · European Respiratory Journal · doi:10.1183/09031936.00077309 · Cited by 477
Self-citationAnimal Models of Fibrotic Lung Disease
Moore, B. B., Lawson, W. E., Oury, T. D., Sisson, T. H., Raghavendran, K., & Hogaboam, C. M. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0094tr · Cited by 434
Danazol Treatment for Telomere Diseases
Townsley, D. M., Dumitriu, B., Liu, D., Biancotto, A., Weinstein, B., Chen, C., Hardy, N., Mihalek, A. D., Lingala, S., Kim, Y. J., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1515319 · Cited by 415
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 450
Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease
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Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive
Newton, C. A., Batra, K., Torrealba, J., Kozlitina, J., Glazer, C. S., Aravena, C., Meyer, K., Raghu, G., Collard, H. R., & Garcia, C. K. (2016) · European Respiratory Journal · doi:10.1183/13993003.00308-2016 · Cited by 400
“Sequencing the TERT, TERC, RTEL1 and PARN genes was performed as previously described [7, 11].”
BackgroundMethodSelf-citationIdiopathic Pulmonary Fibrosis (IPF): An Overview
Barratt, S. L., Creamer, A. W., Hayton, C., & Chaudhuri, N. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7080201 · Cited by 408
“Six telomere-related genes have been linked to familial pulmonary fibrosis (FPF): TERT [30], TERC [58], DKC1 [59], TINF2 [60], RTEL1 [61], and PARN [62], although TERT mutations are most frequent, occurring in approximately 15% those with affected kindreds [63].”
BackgroundAlveolar Epithelial Type II Cells as Drivers of Lung Fibrosis in Idiopathic Pulmonary Fibrosis
Parimon, T., Yao, C., Stripp, B. R., Noble, P. W., & Chen, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072269 · Cited by 397
Telomere Lengths, Pulmonary Fibrosis and Telomerase (TERT) Mutations
Diaz de Leon, A., Cronkhite, J. T., Katzenstein, A.-L. A., Godwin, J. D., Raghu, G., Glazer, C. S., Rosenblatt, R. L., Girod, C. E., Garrity, E. R., Xing, C., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010680 · Cited by 377
“Most of the originally reported TERT mutation cases had IPF, but some did not fit the narrow diagnostic criteria for this disease[18,19].”
BackgroundMethodResultInfluentialSelf-citationMartínez, P., Thanasoula, M., Muñoz, P., Liao, C., Tejera, Á. M., McNees, C. J., Flores, J. M., Fernández-Capetillo, Ó., Tarsounas, M., & Blasco, M. A. (2009) · Genes & Development · doi:10.1101/gad.543509 · Cited by 385
“…distrophy and oral leukoplakia, which are similar to pathologies in human patients with mutations in telomerase components, such as dyskeratosis congenita, aplastic anemia, and some cases of pulmonary fibrosis (Mitchell et al. 1999; Vulliamy et al. 2001; Armanios et al. 2007; Tsakiri et al. 2007).”
BackgroundInfluentialMeiners, S., Eickelberg, O., & Königshoff, M. (2015) · European Respiratory Journal · doi:10.1183/09031936.00186914 · Cited by 340
Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis
Phan, T. H. G., Paliogiannis, P., Nasrallah, G. K., Giordo, R., Eid, A. H., Fois, A. G., Zinellu, A., Mangoni, A. A., & Pintus, G. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03693-7 · Cited by 360
Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis
Kreuter, M., Ehlers-Tenenbaum, S., Palmowski, K., Bruhwyler, J., Oltmanns, U., Muley, T., Heußel, C. P., Warth, A., Kolb, M. R. J., & Herth, F. J. F. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151425 · Cited by 356
“Telomerase mutations in TERT or TERC which cause telomere shortening increase the susceptibility to IPF [33] and there is also considerable evidence that telomere attrition is associated with, and possibly causative of cancer [34] as well as of emphysema [35].”
Backgroundde Jesus, B. B., Schneeberger, K., Vera, E., Tejera, A., Harley, C. B., & Blasco, M. A. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00700.x · Cited by 348
“Further supporting the notion that telomerase levels may be rate-limiting for organismal aging, some diseases characterized by premature loss of tissue renewal and premature death, such as dyskeratosis congenita, aplastic anemia and idiopathic pulmonary fibrosis, are linked to germline mutations in Tert and Terc genes…”
BackgroundTelomeres and age-related disease: how telomere biology informs clinical paradigms
Armanios, M. Y. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66370 · Cited by 352
“Mutant TERT and TR genes account for 8%–15% of familial and 1%–3% of sporadic pulmonary fibrosis cases (45–47).”
Cellular senescence and organismal aging
Jeyapalan, J. C., & Sedivy, J. M. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.04.001 · Cited by 351
Idiopathic Pulmonary Fibrosis: Aberrant Recapitulation of Developmental Programs?
Selman, M., Pardo, A., & Kaminski, N. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050062 · Cited by 342
“Two recent reports demonstrated that mutations in the genes encoding telomerase components are detected in patients with familial IPF, and occasionally in patients with sporadic IPF [59,60].”
BackgroundMinagawa, S., Araya, J., Numata, T., Nojiri, S., Hara, H., Yumino, Y., Kawaishi, M., Odaka, M., Morikawa, T., Nishimura, S. L., et al. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00097.2010 · Cited by 323
Vulliamy, T., Beswick, R., Kirwan, M., Marrone, A., Digweed, M., Walne, A., & Dokal, I. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800042105 · Cited by 334
Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets
Hewlett, J. C., Kropski, J. A., & Blackwell, T. S. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.03.021 · Cited by 334
Epidemiology of idiopathic pulmonary fibrosis
Ley, B., & Collard, H. (2013) · Clinical Epidemiology · doi:10.2147/clep.s54815 · Cited by 321
“These mutations result in shortened telomere lengths in both affected individuals and asymptomatic carriers, and shortened telomere lengths have also been demonstrated in noncarrier family members, suggesting an epigenetic inheritance of short telomeres.(52,53) Also, 25% of sporadic and 37% of familial cases without T…”
Syndromes of Telomere Shortening
Armanios, M. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082908-150046 · Cited by 317
“Germline mutations in hTERT and hTR are also present in 1%–3% of apparently sporadic cases of IPF (2,15,66).”
BackgroundInfluentialStuart, B. D., Lee, J. S., Kozlitina, J., Noth, I., Devine, M. S., Glazer, C. S., Torres, F., Kaza, V., Girod, C. E., Jones, K. D., et al. (2014) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(14)70124-9 · Cited by 310
Self-citationChilosi, M., Carloni, A., Rossi, A., & Poletti, V. E. (2013) · Translational research · doi:10.1016/j.trsl.2013.06.004 · Cited by 319
The Role of Inflammation in the Pathogenesis of Idiopathic Pulmonary Fibrosis
Bringardner, B. D., Baran, C. P., Eubank, T. D., & Marsh, C. B. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1897 · Cited by 324
“Additionally, new insights into the disease, like identifying genetic polymorphisms in genes regulating telomere length in patients with IPF (12, 144) and identifying reduced calveolin-1 in fibroblasts from patients with IPF (150), suggest the dominant role of fibroblast dysfunction in IPF as…”
Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets
Ballester, B., Milara, J., & Cortijo, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030593 · Cited by 318
“Furthermore, the germline variant, rs2736100, has been reported to be associated with lung ADC risk [205], and other TERT, TERC, OFBC1, and RTEL1 polymorphisms have also been revealed as risk factors of LC [206,207].”
BackgroundTPP1 OB-Fold Domain Controls Telomere Maintenance by Recruiting Telomerase to Chromosome Ends
Zhong, F. L., Batista, L. F. Z., Freund, A., Pech, M. F., Venteicher, A. S., & Artandi, S. E. (2012) · Cell · doi:10.1016/j.cell.2012.07.012 · Cited by 308
“The V144M and E1117fsX mutants derive from patients with idiopathic pulmonary fibrosis (Yamaguchi et al., 2005; Armanios et al., 2007; Tsakiri et al., 2007).”
BackgroundLey, B., Newton, C. A., Arnould, I. S., Elicker, B. M., Henry, T. S., Vittinghoff, E., Golden, J. A., Jones, K. D., Batra, K., Torrealba, J. R., et al. (2017) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(17)30216-3 · Cited by 304
Self-citationBiology of Fibroblasts and Myofibroblasts
Phan, S. H. (2008) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200708-146dr · Cited by 299
van Moorsel, C. H. M., van Oosterhout, M. F. M., Barlo, N. P., de Jong, P. A., van der Vis, J. J., Ruven, H. J. T., van Es, H. W., van den Bosch, J. M. M., & Grutters, J. C. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200906-0953oc · Cited by 299
Antoniou, K. M., Margaritopoulos, G. A., Tomassetti, S., Bonella, F., Costabel, U., & Poletti, V. E. (2014) · European Respiratory Review · doi:10.1183/09059180.00009113 · Cited by 294
The pathogenesis of idiopathic pulmonary fibrosis
Coward, W. R., Saini, G., & Jenkins, G. R. (2010) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465810379801 · Cited by 278
“More recently mutations in the TERT gene have been identified in patients with FPF [Armanios et al. 2007; Tsakiri et al. 2007] and subsequently in sporadic IPF [Diaz de Leon et al.”
BackgroundTelomere dysfunction in alveolar epithelial cells causes lung remodeling and fibrosis
Naikawadi, R. P., Disayabutr, S., Mallavia, B., Donne, M. L., Green, G., La, J. L., Rock, J. R., Looney, M. R., & Wolters, P. J. (2016) · JCI Insight · doi:10.1172/jci.insight.86704 · Cited by 267
Telomere Length Is a Determinant of Emphysema Susceptibility
Alder, J. K., Guo, N., Kembou, F., Parry, E. M., Anderson, C. J., Gorgy, A. I., Walsh, M. F., Sussan, T., Biswal, S., Mitzner, W., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201103-0520oc · Cited by 265
“Recent studies in families with IPF have indicated that telomerase mutations play a critical role in the genetics of lung disease(18, 19).”
BackgroundThe therapy of idiopathic pulmonary fibrosis: what is next?
Somogyi, V., Chaudhuri, N., Torrisi, S. E., Kahn, N. C., Müller, V., & Kreuter, M. (2019) · European Respiratory Review · doi:10.1183/16000617.0021-2019 · Cited by 276
Short Telomeres are Sufficient to Cause the Degenerative Defects Associated with Aging
Armanios, M., Alder, J. K., Parry, E. M., Karim, B., Strong, M. A., & Greider, C. W. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.10.028 · Cited by 257
Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita
Zhong, F., Savage, S. A., Shkreli, M., Giri, N., Jessop, L., Myers, T., Chen, R., Alter, B. P., & Artandi, S. E. (2011) · Genes & Development · doi:10.1101/gad.2006411 · Cited by 262
“In patientswith germlinemutations in genes controlling telomere homeostasis, telomere shortening causes a range of disease phenotypes, including dyskeratosis congenita (DC), pulmonary fibrosis, aplastic anemia, and cancer predisposition (Mitchell et al. 1999; Vulliamy et al. 2004; Yamaguchi et al. 2005; Armanios et al…”
BackgroundSavage, S. A., & Alter, B. P. (2009) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2009.01.003 · Cited by 262
“found in patients who had AD and AR DC, in patients who had aplastic anemia and no other signs of DC, and in patients who had pulmonary fibrosis.(18,28,29,30,31,32) The variability in clinical features in patients who had TERC or TERT mutations suggests the”
BackgroundOxidative Stress in Pulmonary Fibrosis
Otoupalova, E., Smith, S., Cheng, G., & Thannickal, V. J. (2020) · Comprehensive physiology · doi:10.1002/cphy.c190017 · Cited by 312
“Telomere shortening and mutations in telomerase genes TERT and TERC have been described in both familial and sporadic forms of IPF (21, 120, 549).”
The genetics and clinical manifestations of telomere biology disorders
Savage, S. A., & Bertuch, A. A. (2010) · Genetics in Medicine · doi:10.1097/gim.0b013e3181f415b5 · Cited by 265
Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology
Levy, D., Neuhausen, S. L., Hunt, S. C., Kimura, M., Hwang, S.-J., Chen, W., Bis, J. C., Fitzpatrick, A. L., Smith, E., Johnson, A. D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911494107 · Cited by 259
Martínez, P., Thanasoula, M., Carlos, A. R., Goméz-López, G., Tejera, Á. M., Schoeftner, S., Domı́nguez, O., Pisano, D. G., Tarsounas, M., & Blasco, M. A. (2010) · Nature Cell Biology · doi:10.1038/ncb2081 · Cited by 273
Diseases of Pulmonary Surfactant Homeostasis
Whitsett, J. A., Wert, S. E., & Weaver, T. E. (2015) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104644 · Cited by 256
Jolly, M. K., Ward, C., Eapen, M. S., Myers, S., Hällgren, O., Levine, H., & Sohal, S. S. (2017) · Developmental Dynamics · doi:10.1002/dvdy.24541 · Cited by 252
A Spectrum of Severe Familial Liver Disorders Associate with Telomerase Mutations
Calado, R. T., Regal, J. A., Kleiner, D. E., Schrump, D. S., Peterson, N. R., Pons, V., Chanock, S. J., Lansdorp, P. M., & Young, N. S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007926 · Cited by 258
“Our current findings parallel the recently reported association of loss-of-function TERT and TERC mutations with familial idiopathic pulmonary fibrosis [12,13].”
BackgroundTelomerase at the intersection of cancer and aging
Bernardes de Jesus, B., & Blasco, M. A. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.06.007 · Cited by 227
Telomerase and idiopathic pulmonary fibrosis
Armanios, M. (2012) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2011.10.013 · Cited by 245
“Among these, IPF/usual interstitial pneumonia is most common seen in approximately 65% of cases[37, 38, 40, 42, 43].”
BackgroundGenetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians
Atzmon, G., Cho, M., Cawthon, R., Budagov, T., Katz, M., Yang, X., Siegel, G., Bergman, A., Huffman, D. M., Schechter, C. B., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906191106 · Cited by 252
“Although these nonsynonymous changes are predicted to be functionally benign, they are also found in idiopathic pulmonary fibrosis (IPF) patients with a MAF >5% (38), raising the possibility that these variants may have negative Table 3.”
BackgroundSelf-citationMushiroda, T., Wattanapokayakit, S., Takahashi, A., Nukiwa, T., Kudoh, S., Ogura, T., Taniguchi, H., Kubo, M., Kamatani, N., & Nakamura, Y. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.057356 · Cited by 247
An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis
Petrovski, S., Todd, J. L., Durheim, M. T., Wang, Q., Chien, J. W., Kelly, F. L., Frankel, C. W., Mebane, C. M., Ren, Z., Bridgers, J., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201610-2088oc · Cited by 244
“The second gene to achieve study-wide Petrovski, Todd, Durheim, et al.: Pulmonary Fibrosis: An Exome Sequencing Study 85 significance was the recently implicated FPF gene RTEL1 (12, 17, 18), with 2.3% of case subjects with pulmonary fibrosis carrying a qualifying variant, as compared with 0% of control subjects (OR, .…”
BackgroundInfluentialEmerging Concepts in the Pathogenesis of Lung Fibrosis
Hardie, W. D., Glasser, S. W., & Hagood, J. S. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081170 · Cited by 244
“Two recent studies demonstrated telomerase mutations (hTERT, hTR) in families with IPF and in some sporadic cases, associated with abnormal telomere length.(101,102) Furthermore, telomerase (TERT)-deficient mice are protected from bleomycin-induced fibrosis; transplantation of wild-type bone marrow into TERT-null mice…”
BackgroundEvans, C. M., Fingerlin, T. E., Schwarz, M. I., Lynch, D. A., Kurche, J. S., Warg, L. A., Yang, I. V., & Schwartz, D. A. (2016) · Physiological Reviews · doi:10.1152/physrev.00004.2016 · Cited by 243
Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report
Blackwell, T. S., Tager, A. M., Borok, Z., Moore, B. B., Schwartz, D. A., Anstrom, K. J., Bar‐Joseph, Z., Bitterman, P. B., Blackburn, M. R., Bradford, W. S., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201306-1141ws · Cited by 243
“telomerase components (49, 90) have similarly been identified in familial and sporadic IPF.”
BackgroundSelf-citationGenetics of human telomere biology disorders
Revy, P., Kannengiesser, C., & Bertuch, A. A. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00527-z · Cited by 250
Podlevsky, J. D., Bley, C. J., Omana, R. V., Qi, X., & Chen, J. J. ‐. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm700 · Cited by 244
“AA and IPF have been linked to mutations in both TERT and TR genes (26,27,32,33).”
BackgroundAhluwalia, N., Shea, B. S., & Tager, A. M. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201403-0509pp · Cited by 237
Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis
Mora, A. L., Bueno, M., & Rojas, M. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci87440 · Cited by 236
Juge, P., Borie, R., Kannengiesser, C., Gazal, S., Revy, P., Wémeau-Stervinou, L., Debray, M., Ottaviani, S., Marchand-Adam, S., Nathan, N., et al. (2017) · European Respiratory Journal · doi:10.1183/13993003.02314-2016 · Cited by 243
Identification of Early Interstitial Lung Disease in Smokers from the COPDGene Study
Washko, G. R., Lynch, D. A., Matsuoka, S., Ross, J. C., Umeoka, S., Díaz, A. A., Sciurba, F. C., Hunninghake, G. M., Estépar, R. S. J., Silverman, E. K., et al. (2009) · Academic Radiology · doi:10.1016/j.acra.2009.07.016 · Cited by 235
“This concept is further supported by family studies demonstrating clustering of ILD cases (19–24) and recent evidence that heterozygous mutations in telomerase reverse transcriptase and telomere shortening are present in up to 8% of kindreds affected with pulmonary fibrosis and may be more frequent in smokers (24,25).”
ResultDuckworth, A., Gibbons, M., Allen, R. J., Almond, H., Beaumont, R. N., Wood, A. R., Lunnon, K., Lindsay, M. A., Wain, L. V., Tyrrell, J., et al. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30364-7 · Cited by 228
Mangino, M., Hwang, S., Spector, T. D., Hunt, S. C., Kimura, M., Fitzpatrick, A. L., Christiansen, L., Petersen, I., Elbers, C. C., Harris, T. B., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds382 · Cited by 228
Actions of human telomerase beyond telomeres
Cong, Y., & Shay, J. W. (2008) · Cell Research · doi:10.1038/cr.2008.74 · Cited by 231
Self-citationThe leading role of epithelial cells in the pathogenesis of idiopathic pulmonary fibrosis
Selman, M., & Pardo, A. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.109482 · Cited by 236
Telomere Dynamics in Mice and Humans
Calado, R. T., & Dumitriu, B. (2013) · Seminars in Hematology · doi:10.1053/j.seminhematol.2013.03.030 · Cited by 214
Telomere maintenance and human bone marrow failure
Calado, R. T., & Young, N. S. (2008) · Blood · doi:10.1182/blood-2007-08-019729 · Cited by 227
“Among the seven families and the sporadic case of pulmonary fibrosis, smoke exposure was noted in 60% of affected individuals.(94) Hepatic cirrhosis has been described in dyskeratosis congenita, and severe liver disease is not uncommon after hematopoietic stem cell transplant for marrow failure in patients with this c…”
BackgroundInfluentialThe Rate of Increase of Short Telomeres Predicts Longevity in Mammals
Vera, E., de Jesus, B. B., Foronda, M., Flores, J. M., & Blasco, M. A. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.08.023 · Cited by 228
“In further support of this notion, both telomerase-deficient mice and human diseases due to mutations in telomerase components result in accelerated-aging phenotypes and decreased longevity due to premature depletion of stem cells and subsequent organ/tissue failure (Armanios et al., 2007; Blasco et al., 1997; Garcı́a…”
BackgroundA ‘higher order’ of telomere regulation: telomere heterochromatin and telomeric RNAs
Schoeftner, S., & Blasco, M. A. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.197 · Cited by 232
“…human syndromes such as Aplastic anaemia (TERC, TERT) (Yamaguchi et al, 2005), Dyskeratosis congenita (DKC1, TERC) and idiopatic pulmonary fibrosis (Tsakiri et al, 2007), or by mutations in various DNA repair genes such as Ataxia telangiectasia (ATM), Werner (WRN) and Bloom syndromes (BLM),…”
Background
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
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