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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- 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
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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
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Oxidative stress shortens telomeres
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Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
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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
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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
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Cited by
Sorted by citations
Items 401–500 of 892
Revealing the Secrets of Idiopathic Pulmonary Fibrosis
Albert, R. K., & Schwartz, D. A. (2019) · New England Journal of Medicine · doi:10.1056/nejmcibr1811639 · Cited by 39
Trade-offs in aging lung diseases
van Moorsel, C. H. M. (2018) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000476 · Cited by 40
Alcaraz‐Pérez, F., García‐Castillo, J., García‐Moreno, D., López‐Muñoz, A., Anchelin, M., Angosto-Bazarra, D., Zon, L. I., Mulero, V., & Cayuela, M. L. (2014) · Nature Communications · doi:10.1038/ncomms4228 · Cited by 41
Role of Mesenchymal Stem Cells and Extracellular Vesicles in Idiopathic Pulmonary Fibrosis
Kletukhina, S. K., Mutallapova, G., Андреевна, Т. А., & Gomzikova, M. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911212 · Cited by 38
Gramatges, M. M., Qi, X., Sasa, G., Chen, J. J. ‐., & Bertuch, A. A. (2013) · Blood · doi:10.1182/blood-2012-08-447755 · Cited by 38
The Role of Aging in Idiopathic Pulmonary Fibrosis
Leung, J., Cho, Y. S., Lockey, R. F., & Kolliputi, N. (2015) · Lung · doi:10.1007/s00408-015-9729-3 · Cited by 38
“However, as a person ages, it has been found that the activity of telomerase decreases which increases the rate at which telomeres are damaged [39].”
BackgroundTelomere Abnormalities in the Pathobiology of Idiopathic Pulmonary Fibrosis
Bilgili, H., Białas, A. J., Górski, P., & Piotrowski, W. J. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8081232 · Cited by 39
“reported that the mean age of death of the smokers with a mutation in TERT or TERC was 10 years earlier than that of the nonsmokers [38].”
BackgroundInfluentialHuman Telomerase RNA: Telomerase Component or More?
Rubtsova, M. P., & Донцова, О. А. (2020) · Biomolecules · doi:10.3390/biom10060873 · Cited by 38
“Mutations in hTERT and hTERC genes are involved in the development of diseases linked to dysfunctional telomeres, such as aplastic anemia, the autosomal dominant form of dyskeratosis congenita [15–17], and idiopathic pulmonary fibrosis [18].”
BackgroundInsights from human genetic studies of lung and organ fibrosis
Garcia, C. K. (2018) · Journal of Clinical Investigation · doi:10.1172/jci93556 · Cited by 37
“The gene defects in telomerase (TERT, TERC) were first described in kindreds in whom pulmonary fibrosis segregated in an autosomal dominant pattern with incomplete penetrance (18, 19).”
BackgroundSelf-citationMattoo, H., & Pillai, S. S. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03874-y · Cited by 38
Gansner, J. M., & Rosas, I. O. (2013) · Translational research · doi:10.1016/j.trsl.2013.04.001 · Cited by 38
Miles, T., Hoyne, G. F., Knight, D. A., Fear, M. W., Mutsaers, S. E., & Prêle, C. M. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1153 · Cited by 37
Hong, X., Wang, L., Zhang, K., Liu, J., & Liu, J. (2022) · Cells · doi:10.3390/cells11050877 · Cited by 37
Medical genetics and epigenetics of telomerase
Koziel, J. E., Fox, M. J., Steding, C. E., Sprouse, A. A., & Herbert, B. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01276.x · Cited by 37
Hoffman, H., Rice, C., & Skordalakes, E. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.771204 · Cited by 37
“DKC patients are also high risk for IPF, a disease associated with lung scaring and decrease in oxygen transport to the body (24).”
BackgroundIrvine, A. D., & Mellerio, J. E. (2010) · Wiley eBooks · doi:10.1002/9781444317633.ch15 · Cited by 35
Cloning a profibrotic stem cell variant in idiopathic pulmonary fibrosis
Wang, S., Rao, W. H., Hoffman, A., Lin, J. M., Li, J., Lin, T., Liew, A.-A., Vincent, M., Mertens, T. C. J., Karmouty‐Quintana, H., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abp9528 · Cited by 35
Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium
Bridges, J. P., Vladar, E. K., Kurche, J. S., Krivoi, A., Stancil, I. T., Dobrinskikh, E., Hu, Y., Sasse, S. K., Lee, J. S., Blumhagen, R. Z., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci183836 · Cited by 41
“Genetic variants in the telomere synthesis enzymes TERT and TERC (144, 152) have also been implicated in IPF (150, 153–158), and sporadic mutations in telomere-supporting shelterin proteins have also been”
Development of Lysophosphatidic Acid Pathway Modulators as Therapies for Fibrosis
Budd, D. C., & Qian, Y. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.154 · Cited by 35
Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations
Nakamura, Y., & Suda, T. (2015) · Clinical Medicine Insights Circulatory Respiratory and Pulmonary Medicine · doi:10.4137/ccrpm.s39897 · Cited by 40
Involvement of midkine in the development of pulmonary fibrosis
Misa, K., Tanino, Y., Wang, X., Nikaido, T., Kikuchi, M., Sato, Y., Togawa, R., Tanino, M. A., Tanaka, S., Kadomatsu, K., et al. (2017) · Physiological Reports · doi:10.14814/phy2.13383 · Cited by 34
“2011) and telomere-related genes (Armanios et al. 2007; Tsakiri et al. 2007), and repeated DNA damage by excessive reactive-oxygen species (Kinnula et al.”
BackgroundWhole exome sequencing analysis in severe chronic obstructive pulmonary disease
Qiao, D., Ameli, A., Prokopenko, D., Chen, H., Kho, A. T., Parker, M. M., Morrow, J. D., Hobbs, B. D., Liu, Y., Beaty, T. H., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy269 · Cited by 34
Shimbori, C., Bellaye, P., Kolb, P., & Kolb, M. R. J. (2017) · Milestones in drug therapy · doi:10.1007/978-3-0348-0977-1_3 · Cited by 38
Piñeiro‐Hermida, S., Martínez, P., Bosso, G., Flores, J. M., Saraswati, S., Connor, J. R., Lemaire, R., & Blasco, M. A. (2022) · Nature Communications · doi:10.1038/s41467-022-32771-6 · Cited by 37
Clinical implications of telomere dysfunction in lung fibrosis
Molina‐Molina, M., & Borie, R. (2018) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000506 · Cited by 37
Thannickal, V. J., & Loyd, J. E. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200807-1127ed · Cited by 35
“Armanios and colleagues’ verified their hypothesis by demonstrating mutations in TERT, and in the RNA component of telomerase, in six families with IPF (4), and soon thereafter nearly identical findings were described by the authors of the current report in another seven families (5).”
ResultGenomics of Human Fibrotic Diseases: Disordered Wound Healing Response
Stone, R. C., Chen, V., Burgess, J. L., Pannu, S., & Tomic‐Canic, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228590 · Cited by 35
Beghé, B., Cerri, S., Fabbri, L. M., & Marchioni, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179292 · Cited by 33
“In patients with both familial and sporadic IPF, diminished telomerase activity and prematurely shortened telomere length (TL) have been found in blood leukocytes regardless of the presence of genetic mutations in TERT (Telomerase Reverse Transcriptase) and/or in TERC (telomerase RNA component) [57].”
BackgroundIdiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine
Alonso-González, A., Tosco-Herrera, E., Molina‐Molina, M., & Flores, C. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1152211 · Cited by 36
Lu, W., Teoh, A. K. Y., Waters, M., Haug, G., Shakeel, I., Hassan, M. I., Shahzad, A. M., Larsson‐Callerfelt, A., Piccari, L., & Sohal, S. S. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108757 · Cited by 35
Understanding telomere diseases through analysis of patient-derived iPS cells
Batista, L. F. Z., & Artandi, S. E. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.07.006 · Cited by 35
Incorporating genetics into the identification and treatment of Idiopathic Pulmonary Fibrosis
Mathai, S. K., Yang, I. V., Schwarz, M. I., & Schwartz, D. A. (2015) · BMC Medicine · doi:10.1186/s12916-015-0434-0 · Cited by 34
“compared to age-matched family members without mutations [22].”
ResultClinical features of interstitial pneumonia associated with systemic lupus erythematosus
Toyoda, Y., Koyama, K., Kawano, H., Nishimura, H., Kagawa, K., Morizumi, S., Naito, N., Sato, S., Yamashita, Y., Takahashi, N., et al. (2019) · Respiratory Investigation · doi:10.1016/j.resinv.2019.04.005 · Cited by 36
Long non-coding RNAs at work on telomeres: Functions and implications in cancer therapy
Gala, K., & Khattar, E. (2021) · Cancer Letters · doi:10.1016/j.canlet.2020.12.036 · Cited by 34
van Batenburg, A. A., Kazemier, K. M., van Oosterhout, M. F. M., van der Vis, J. J., Grutters, J. C., Goldschmeding, R., & van Moorsel, C. H. M. (2021) · ERJ Open Research · doi:10.1183/23120541.00691-2020 · Cited by 36
Aschner, Y., Khalifah, A. P., Briones, N. J., Yamashita, C. M., Dolgonos, L., Young, S. K., Campbell, M., Riches, D. W. H., Redente, E. F., Janssen, W. J., et al. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.01.016 · Cited by 32
IDIOPATHIC PULMONARY FIBROSIS IS A COMPLEX GENETIC DISORDER.
Schwartz, D. A. (2016) · PubMed Central · Cited by 33
Cell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status
Song, Z., Ju, Z., & Rudolph, K. L. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.06.009 · Cited by 34
“Lastly, mutations in human telomerase genes lead to telomere shortening, stem cell defects, impaired organ maintenance and a shortened lifespan (Armanios et al., 2007; Tsakiri et al., 2007; Vulliamy et al., 2004).”
BackgroundGenetic “lnc”-age of noncoding RNAs to human disease
Troy, A., & Sharpless, N. E. (2012) · Journal of Clinical Investigation · doi:10.1172/jci66645 · Cited by 32
Aging, antagonistic pleiotropy and fibrotic disease
Thannickal, V. J. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.05.010 · Cited by 32
van Batenburg, A. A., Kazemier, K. M., van Oosterhout, M. F. M., van der Vis, J. J., van Es, H. W., Grutters, J. C., Goldschmeding, R., & van Moorsel, C. H. M. (2020) · PLoS ONE · doi:10.1371/journal.pone.0226785 · Cited by 34
Mesenchymal Stem Cell Therapy and Lung Diseases
Akram, K. M., Samad, S., Spiteri, M. A., & Forsyth, N. R. (2012) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2012_140 · Cited by 33
Jackson, S.-R., Lee, J., Reddy, R., Williams, G. N., Kikuchi, A., Freiberg, Y., Warburton, D., & Driscoll, B. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00409.2010 · Cited by 32
“In lung, telomerase mutations have been linked to idiopathic pulmonary fibrosis of the lung (IPF) (2, 4, 22, 57), a condition hypothesized to be initiated in some cases by epithelial hypoplasia (35, 53).”
BackgroundTargeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis
Deng, Y., Li, Z., Liu, J., Wang, Z., Cao, Y., Mou, Y., Fu, B., Mo, B., Wei, J., Cheng, Z., et al. (2018) · Human Mutation · doi:10.1002/humu.23566 · Cited by 32
“According to previous studies, pathogenic variants of TERT and TERC occur in approximately 8%–15% of FPF and 1%–3% of sporadic IPF patients (Armanios et al., 2007; Tsakiri et al., 2007).”
BackgroundInherited bone marrow failure syndromes in 2012
Sakaguchi, H., Nakanishi, K., & Kojima, S. (2012) · International Journal of Hematology · doi:10.1007/s12185-012-1249-9 · Cited by 32
“Mutations in telomerase and telomere components have also been identified in patients with aplastic anemia, pulmonary fibrosis, and liver diseases that did not have any mucocutaneous manifestations [45, 46, 51–59].”
BackgroundDodson, L. M., Baldan, A., Nissbeck, M., Gunja, S. M. R., Bonnen, P. E., Aubert, G., Birchansky, S. B., Virtanen, A., & Bertuch, A. A. (2019) · Human Mutation · doi:10.1002/humu.23898 · Cited by 35
Phillips-Houlbracq, M., Mal, H., Cottin, V., Gauvain, C., Beier, F., de Fontbrune, F. S., Sidali, S., Mornex, J., Hirschi, S., Roux, A., et al. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16893 · Cited by 34
Dyskerin, telomerase and the DNA damage response
Gu, B.-W., Bessler, M., & Mason, P. J. (2009) · Cell Cycle · doi:10.4161/cc.8.1.7265 · Cited by 31
Short and dysfunctional telomeres sensitize the kidneys to develop fibrosis
Saraswati, S., Martínez, P., Graña-Castro, O., & Blasco, M. A. (2021) · Nature Aging · doi:10.1038/s43587-021-00040-8 · Cited by 28
Advances in cellular senescence in idiopathic pulmonary fibrosis (Review)
Han, S., Lu, Q., & Liu, X. (2023) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2023.11844 · Cited by 32
“…in IPF patients, so as to further understand the role of naturally occurring telomerase mutations in the pathophysiology of some age‑related disease states; in vitro experiments have determined that V144 and R865 in hTRT are key residues required for the normal function of cell telomerase (36,37).”
Zolak, J. S., & de Andrade, J. A. (2012) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2012.08.006 · Cited by 32
Novel idiopathic pulmonary fibrosis susceptibility variants revealed by deep sequencing
Lorenzo-Salazar, J. M., Ma, S., Jou, J., Hou, P., Guillén‐Guío, B., Allen, R. J., Jenkins, G. R., Wain, L. V., Oldham, J. M., Noth, I., et al. (2019) · ERJ Open Research · doi:10.1183/23120541.00071-2019 · Cited by 31
Pathology, Radiology, and Genetics of Interstitial Lung Disease in Patients With Shortened Telomeres
Cecchini, M. J., Tarmey, T., Ferreira, A. J., Mangaonkar, A. A., Ferrer, A., Patnaik, M. M., Wylam, M. E., Jenkins, S. M., Spears, G. M., Yi, E. S., et al. (2021) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001725 · Cited by 29
Telomere dysfunction in human diseases: the long and short of it!
Carroll, K. A., & Ly, H. (2009) · Europe PMC (PubMed Central) · Cited by 30
Dalby, A. B., Hofr, C., & Cech, T. R. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.01.008 · Cited by 31
“The mutation in hTERT V144M associated with idiopathic pulmonary fibrosis [57] has deficiencies in RAP stimulation by wild-type TPP1-POT1 [40], as well as in vivo telomere localization [37].”
Liu, T., Yu, H., Ding, L., Wu, Z. B., Santos, F. G. D. L., Liu, J., Ullenbruch, M. R., Hu, B., Martins, V., & Phan, S. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142547 · Cited by 33
“Moreover lung fibroblasts from animal models and most patients with IPF do not exhibit shortened telomeres, while shortened telomeres in late generation TERC deficient mice are not associated with increased susceptibility to BLM-induced pulmonary fibrosis [33].”
BackgroundInfluentialTelomere biology of the chicken: A model for aging research
Swanberg, S. E., O’Hare, T. H., Robb, E. A., Robinson, C. M., Chang, H., & Delany, M. E. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.04.002 · Cited by 32
Li, C., Wei, R., Jones‐Hall, Y., Vittal, R., Zhang, M., & Liu, W. (2014) · Scientific Reports · doi:10.1038/srep04893 · Cited by 29
Pulmonary endoplasmic reticulum stress—scars, smoke, and suffocation
Dickens, J. A., Malzer, E., Chambers, J. E., & Marciniak, S. J. (2018) · FEBS Journal · doi:10.1111/febs.14381 · Cited by 29
Tousif, S., Wang, Y., Jackson, J. D., Hough, K. P., Strenkowski, J. G., Athar, M., Thannickal, V. J., McCusker, R. H., Ponnazhagan, S., & Deshane, J. S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.747780 · Cited by 30
Xu, X., Dai, H., & Wang, C. (2014) · The Clinical Respiratory Journal · doi:10.1111/crj.12190 · Cited by 29
“It is suggested that AECs ageing and senescence caused by telomerase mutations may account for the impaired ability to re-epithelialize an intact alveoli (60).”
BackgroundMultiple genetic pathways regulate replicative senescence in telomerase‐deficient yeast
Ballew, B. J., & Lundblad, V. (2013) · Aging Cell · doi:10.1111/acel.12099 · Cited by 28
Genetic Predisposition to Respiratory Diseases: Infiltrative Lung Diseases
Steele, M. P., & Brown, K. K. (2006) · Respiration · doi:10.1159/000110204 · Cited by 30
“Using 6 pedigrees, associations on chromosomes 3 (marker D3S1278), 4 (marker D4S424) and 13 (D13S265) were obtained. On chromosome 4, a shared haplotype was identified among 8 of 24 multiplex families. A candidate gene located in the region of interest, ELMOD2, was further investigated by resequencing of exons and exo…”
BackgroundInfluentialThe Lung: The Natural Boundary Between Nature and Nurture
Seibold, M. A., & Schwartz, D. A. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142212 · Cited by 27
Understanding idiopathic pulmonary fibrosis - Clinical features, molecular mechanism and therapies
Suri, G. S., Kaur, G., Jha, C. K., & Tiwari, M. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111473 · Cited by 29
Hecker, L., & Thannickal, V. J. (2011) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31821a9d66 · Cited by 29
Waisberg, D. R., Parra, E. R., Barbas‐Filho, J. V., Fernezlian, S., & Capelozzi, V. L. (2012) · Clinics · doi:10.6061/clinics/2012(09)10 · Cited by 28
“In light of these (10) and other recent findings implicating telomerase in IPF pathogenesis (11-14), we sought to study”
BackgroundWang, J., & Chao, J. (2025) · Pharmaceuticals · doi:10.3390/ph18060812 · Cited by 31
A structurally conserved human and Tetrahymena telomerase catalytic core
Wang, Y., Gallagher-Jones, M., Sušac, L., Song, H., & Feigon, J. F. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2011684117 · Cited by 27
“Several mutations in the IFD-TRAP are associated with diseases of telomerase insufficiency, including dyskeratosis congenita [M773T (53), V777L (54), R811C (55)], bone marrow failure [Q722X (56)], idiopathic pulmonary fibrosis [R742H (57), V747A (58), V777L (54)], aplastic anemia [T726M (59), Y772C (60)], and acute my…”
BackgroundVenosa, A., Cowman, S. J., Katzen, J. B., Tomer, Y., Armstrong, B. S., Mulugeta, S., & Beers, M. F. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.665818 · Cited by 28
Plasticity towards Rigidity: A Macrophage Conundrum in Pulmonary Fibrosis
Sari, E., He, C., & Margaroli, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911443 · Cited by 28
Ecogenomics of Respiratory Diseases of Public Health Significance
Garantziotis, S., & Schwartz, D. A. (2010) · Annual Review of Public Health · doi:10.1146/annurev.publhealth.012809.103633 · Cited by 27
“Missense mutations in surfactant protein A2 (SFTPA2) were detected in two of 59 FIP kindreds (89) who presented with early-onset pulmonary fibrosis and/or lung cancer.”
BackgroundInfluentialAuld, S. C., Sheshadri, A., Alexander‐Brett, J. M., Aschner, Y., Barczak, A. K., Basil, M. C., Cohen, K. A., Cruz, C. S. D., McGroder, C. F., Restrepo, M. I., et al. (2024) · Annals of the American Thoracic Society · doi:10.1513/annalsats.202406-651st · Cited by 28
“Of the genetic factors associated with IPF, telomere shortening (251, 252), with or without rare telomere mutations (253, 254), and the MUC5B promoter polymorphism rs35705950 (51) may also play a role in fi brosis associated with COVID-19.”
Clinical Genetics in Interstitial Lung Disease
Newton, C. A., Molyneaux, P. L., & Oldham, J. M. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00116 · Cited by 27
“Studying large families with multiple affected members led to the discovery of multiple genes associated with monogenetic forms of familial pulmonary fibrosis (FPF) and improved our understanding of the genetic underpinnings of ILD.”
BackgroundInfluentialClinical Impact of Telomere Length Testing for Interstitial Lung Disease
Zhang, D., Eckhardt, C. M., McGroder, C. F., Benesh, S., Porcelli, J., Depender, C., Bogyo, K., Westrich, J. A., Thomas‐Wilson, A., Jobanputra, V., et al. (2024) · CHEST Journal · doi:10.1016/j.chest.2024.06.006 · Cited by 26
Self-citationEmerging drugs for idiopathic pulmonary fibrosis
Selman, M., Pardo, A., Richeldi, L., & Cerri, S. (2011) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2011.565049 · Cited by 26
“Heterozygous loss-offunction mutations in the human telomerase genes have been associated in close to 10% of familial IPF [41-43].”
BackgroundNovel variants in Nordic patients referred for genetic testing of telomere-related disorders
Norberg, A., Rosén, A., Raaschou‐Jensen, K., Kjeldsen, L., Moilanen, J. S., Paulsson-Karlsson, Y., Baliakas, P., Lohi, O., Ahmed, A. B., Kittang, A. O., et al. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-018-0112-8 · Cited by 26
“Other telomere-related disorders include Hoyeraal–Hreidarsson syndrome (HHS) [10], pulmonary fibrosis (PF) [11, 12], aplastic anemia (AA) [13, 14], myelodysplastic syndrome (MDS) [15], acute myeloid leukemia (AML) [16], and liver cirrhosis [17, 18].”
Mutairy, E. A., Imtiaz, F., Khalid, M., Qattan, S. M. A., Saleh, S. M., Mahmoud, L., Al‐Saif, M., Al‐Haj, L., Al-Enazi, A. A., Aljebreen, A., et al. (2019) · European Respiratory Journal · doi:10.1183/13993003.02041-2018 · Cited by 25
The world of rare interstitial lung diseases
Buschulte, K., Cottin, V., Wijsenbeek, M. S., Kreuter, M., & Diesler, R. (2023) · European Respiratory Review · doi:10.1183/16000617.0161-2022 · Cited by 26
Genetic and environmental factors influencing human diseases with telomere dysfunction.
Ly, H. (2009) · PubMed · Cited by 25
The importance of matrix metalloproteinase-3 in respiratory disorders
Yamashita, C. M., Radisky, D. C., Aschner, Y., & Downey, G. P. (2014) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2014.909288 · Cited by 26
Magnini, D., Montemurro, G., Iovene, B., Tagliaboschi, L., Gerardi, R. E., Greco, E. L., Bruni, T., Fabbrizzi, A., Lombardi, F., & Richeldi, L. (2017) · Respiration · doi:10.1159/000475780 · Cited by 25
The Role of Toll-like Receptors in Age-Associated Lung Diseases
Volkova, M., Zhang, Y., Shaw, A. C., & Lee, C. G. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr226 · Cited by 26
“For example, genome analysis revealed mutations in telomerase, an enzyme that protects telomeres from damage and whose activity declines with age (50).”
BackgroundEvidence of telomere attrition and a potential role for DNA damage in systemic sclerosis
Usategui, A., Municio, C., Arias‐Salgado, E. G., Martín, M. J., Fernández-Varas, B., Rey, M. J. D., Carreira, P. E., Gonzalez, A., Criado, G., Perona, R., et al. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00263-2 · Cited by 24
“Mutations of telomerase and shelterin genes are associated with TS and represent the most common genetic factor associated with familial idiopathic pulmonary fibrosis and less frequently with sporadic forms of adult-onset pulmonary fibrosis [3, 4].”
BackgroundClé, D. V., Catto, L. F. B., Gutierrez‐Rodrigues, F., Donaires, F. S., Pinto, A. L., Santana, B. A., Darrigo, L. G., Valera, E. T., Santos, M. K., Martínez, J. A. B., et al. (2022) · Haematologica · doi:10.3324/haematol.2022.281808 · Cited by 24
“Age in years, median (range) 36 (4-59) 40 (21-59) 34 (10-54) 12 30 4 40 (18-40)”
Personalized Medicine: Applying ‘omics’ to Lung Fibrosis
Herazo‐Maya, J. D., & Kaminski, N. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.38 · Cited by 24
Antoniou, K. M., Margaritopoulos, G. A., Proklou, Α., Karagiannis, K., Lasithiotaki, I., Soufla, G., Kastrinaki, M.-C., Spandidos, D. A., Papadaki, H. Α., & Siafakas, N. M. (2012) · Journal of Inflammation · doi:10.1186/1476-9255-9-27 · Cited by 24
“It was observed that mutations in both components of telomerase are present in 8-15% of patients with familial IPF [35,36].”
Idiopathic pulmonary fibrosis: treatment options in pursuit of evidence-based approaches
Raghu, G. (2006) · European Respiratory Journal · doi:10.1183/09031936.06.00086606 · Cited by 24
Self-citationNew trajectories in the treatment of interstitial lung disease
Morisset, J., & Lee, J. S. (2019) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000600 · Cited by 23
Fang, C., Huang, H. F., Zhang, Q., Wang, N., Jing, X., Guo, J., Ferianc, M., & Xu, Z. (2020) · Respirology · doi:10.1111/resp.13871 · Cited by 23
Distinguishing constitutional from acquired bone marrow failure in the hematology clinic
Groarke, E. M., Young, N. S., & Calvo, K. R. (2021) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2021.101275 · Cited by 25
Wang, P., Leung, J., Lam, A., Lee, S., Calabrese, D. R., Hays, S. R., Golden, J. A., Kukreja, J., Singer, J. P., Wolters, P. J., et al. (2021) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2021.11.012 · Cited by 24
Philippot, Q., Kannengiesser, C., Debray, M., Gauvain, C., Ba, I., Vieri, M., Gondouin, A., Naccache, J., Reynaud‐Gaubert, M., Uzunhan, Y., et al. (2022) · Respirology · doi:10.1111/resp.14195 · Cited by 25
Multisystemic Manifestations in Rare Diseases: The Experience of Dyskeratosis Congenita
Callea, M., Martinelli, D., Cammarata-Scalisi, F., Grimaldi, C., Jilani, H., Grimaldi, P., Willoughby, C. E., & Morabito, A. (2022) · Genes · doi:10.3390/genes13030496 · Cited by 25
“Other disease manifestations are pulmonary fibrosis [12] and liver failure or fibrosis [13].”
BackgroundWilson, K. A., Chateau, M., & Porteus, M. H. (2013) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2013.12 · Cited by 23
Ueda, Y., Calado, R. T., Norberg, A., Kajigaya, S., Roos, G., Hellström‐Lindberg, E., & Young, N. S. (2014) · BMC Medical Genetics · doi:10.1186/1471-2350-15-68 · Cited by 24
“in the TERC gene as well as in other telomerase components cause accelerated telomere attrition, leading to disease: dyskeratosis congenita mainly in children [10-15], pulmonary fibrosis [16-18], liver cirrhosis [19], and bone marrow failure syndromes of adults (aplastic anemia, myelodysplastic syndromes (MDS), and ot…”
BackgroundPersonalised medicine in interstitial lung diseases
Kokosi, M. A., Margaritopoulos, G. A., & Wells, A. U. (2018) · European Respiratory Review · doi:10.1183/16000617.0117-2017 · Cited by 23
Halu, A., Liu, S., Baek, S. H., Hobbs, B. D., Hunninghake, G. M., Cho, M. H., Silverman, E. K., & Sharma, A. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz069 · Cited by 22
“Telomere maintenance is important in cell aging (senescence), cell division and cell survival, and telomererelated genes are highly associated with IPF (34), though they are also associated with COPD (35); (ii) COPD-up pathways that are highly prioritized with respect to IPF-down module (Table 2, lower left quadrant),…”
BackgroundGenetic architecture of human fibrotic diseases: disease risk and disease progression
Gardet, A., Zheng, T. S., & Viney, J. L. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00159 · Cited by 23
Telomeres do the (un)twist: Helicase actions at chromosome termini
Chavez, A., Tsou, A. M., & Johnson, F. B. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.02.008 · Cited by 24
“Similarly, people with other hypomorphic mutations in telomerase, or short telomeres in the absence of an apparent telomerase mutation, are at increased risk for bone marrow failure, pulmonary fibrosis and liver cirrhosis [35-38].”
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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