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.
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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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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.”
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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).”
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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).”
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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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In the paper
“Four additional sequence variations, including three missense mutations and one 177-bp deletion, were found (Fig. 3).”
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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
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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.”
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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.”
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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.”
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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
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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
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In the paper
“One proband of a Caucasian family (F61) was heterozygous for an adenosine and guanine at position 37.”
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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
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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
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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
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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.”
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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.”
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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
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In the paper
“Pulmonary fibrosis appears to be a human-specific manifestation of telomerase deficiency.”
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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.”
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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.”
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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
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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
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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.”
Tests✓ Asserted: passes? Checkable: unclear✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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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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In the paper
“This study was approved by the University of Texas Southwestern Institutional Review Board. Written informed consent was obtained from all participants.”
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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.”
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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
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(2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.2.ats01 · Cited by 4,196
Merlin—rapid analysis of dense genetic maps using sparse gene flow trees
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Oxidative stress shortens telomeres
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Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
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Telomere reduction in human colorectal carcinoma and with ageing
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Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
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Incidence and Prevalence of Idiopathic Pulmonary Fibrosis
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Self-citationIdiopathic Pulmonary Fibrosis: Clinical Relevance of Pathologic Classification
KATZENSTEIN, A.-L. A., & MYERS, J. L. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.4.9707039 · Cited by 1,261
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Review: a meta‐analysis of GWAS and age‐associated diseases
Jeck, W. R., Siebold, A. P., & Sharpless, N. E. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00871.x · Cited by 204
“33 bin was also associated with idiopathic pulmonary fibrosis (IPF), consistent with the finding of increased IPF in patients with congenital telomerase deficiency (Armanios et al., 2007; Tsakiri et al., 2007).”
BackgroundThe 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia
Hsiung, C. A., Lan, Q., Hong, Y., Chen, C., Hosgood, H. D., Chang, I., Chatterjee, N., Brennan, P., Wu, C. H., Zheng, W., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001051 · Cited by 211
“Mutations in the TERT gene have also been described in patients with idiopathic pulmonary fibrosis [30,31].”
BackgroundDoes Chronic Microaspiration Cause Idiopathic Pulmonary Fibrosis?
Lee, J. S., Collard, H. R., Raghu, G., Sweet, M. P., Hays, S. R., Campos, G. M., Golden, J. A., & King, T. E. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.07.033 · Cited by 215
Self-citationBallew, B. J., & Savage, S. A. (2013) · Expert Review of Hematology · doi:10.1586/ehm.13.23 · Cited by 214
Stanley, S. E., Gable, D. L., Wagner, C. L., Carlile, T. M., Hanumanthu, V. S., Podlevsky, J. D., Khalil, S. E., Dezern, A. E., Rojas-Durán, M. F., Applegate, C. D., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf7837 · Cited by 214
Time for a change: is idiopathic pulmonary fibrosis still idiopathic and only fibrotic?
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Self-citationBaseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis
Ohshimo, S., Ishikawa, N., Horimasu, Y., Hattori, N., Hirohashi, N., Tanigawa, K., Kohno, N., Bonella, F., Guzman, J., & Costabel, U. (2014) · Respiratory Medicine · doi:10.1016/j.rmed.2014.04.009 · Cited by 202
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The genetic basis of idiopathic pulmonary fibrosis
Kropski, J. A., Blackwell, T. S., & Loyd, J. E. (2015) · European Respiratory Journal · doi:10.1183/09031936.00163814 · Cited by 193
Rare Variants in RTEL1 Are Associated with Familial Interstitial Pneumonia
Cogan, J. D., Kropski, J. A., Zhao, M., Mitchell, D. B., Rives, L. C., Markin, C. R., Garnett, E. T., Montgomery, K. H., Mason, W. R., McKean, D. F., et al. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201408-1510oc · Cited by 203
“Previous studies using linkage and candidate gene approaches have identified rare heterozygous mutations in surfactant protein A2 (SFTPA2) (4), surfactant protein C (SFTPC) (5, 6), telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) (7, 8), and dyskerin (DKC1) (9, 10) that account for at most 10–1…”
BackgroundInfluentialDressen, A., Abbas, A. R., Cabanski, C. R., Reeder, J., Ramalingam, T. R., Neighbors, M., Bhangale, T., Brauer, M. J., Hunkapiller, J., Reeder, J., et al. (2018) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(18)30135-8 · Cited by 196
Mechanisms of development of multimorbidity in the elderly
Barnes, P. J. (2015) · European Respiratory Journal · doi:10.1183/09031936.00229714 · Cited by 204
Parry, E. M., Alder, J. K., Qi, X., Chen, J. J.-L., & Armanios, M. (2011) · Blood · doi:10.1182/blood-2010-11-322149 · Cited by 194
Telomeres in cancer and ageing
Donate, L. E., & Blasco, M. A. (2010) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2010.0291 · Cited by 199
Constitutional telomerase mutations are genetic risk factors for cirrhosis
Calado, R. T., Brudno, J. N., Chaudhry, P. M., Kovacs, J. J., Wu, C. O., Zago, M. A., Chanock, S. J., BOYER, T. D., & Young, N. S. (2011) · Hepatology · doi:10.1002/hep.24173 · Cited by 195
“In agreement with our findings, in families with idiopathic pulmonary fibrosis and telomerase mutations, short telomeres have been hypothesized to limit pneumocyte proliferation, causing loss of alveolar cells and, secondarily, fibrosis.(12,13) Alternatively, in cirrhosis, short telomeres may affect stellate cell diff…”
BackgroundResultConstitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia
Calado, R. T., Regal, J. A., Hills, M., Yewdell, W. T., Dalmazzo, L. F., Zago, M. A., Lansdorp, P. M., Hogge, D., Chanock, S. J., Estey, E. H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807057106 · Cited by 184
“Idiopathic pulmonary fibrosis also is associated with telomerase mutations (12, 13); as many as 20% of DKC patients develop pulmonary fibrosis (14).”
BackgroundPrevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis
Borie, R., Tabèze, L., Thabut, G., Nunès, H., Cottin, V., Marchand-Adam, S., Prévôt, G., Tazi, A., Cadranel, J. L., Mal, H., et al. (2016) · European Respiratory Journal · doi:10.1183/13993003.02115-2015 · Cited by 199
The pathogenesis of COPD and IPF: Distinct horns of the same devil?
Chilosi, M., Poletti, V. E., & Rossi, A. (2012) · Respiratory Research · doi:10.1186/1465-9921-13-3 · Cited by 187
“senescence and lung “premature aging” [19-33].”
Poly(A)-specific ribonuclease (PARN) mediates 3′-end maturation of the telomerase RNA component
Moon, D. H., Segal, M., Boyraz, B., Guinan, E. C., Hofmann, I., Cahan, P., Tai, A., & Agarwal, S. (2015) · Nature Genetics · doi:10.1038/ng.3423 · Cited by 192
Exome Sequencing Identifies Mutant TINF2 in a Family With Pulmonary Fibrosis
Alder, J. K., Stanley, S. E., Wagner, C. L., Hamilton, M., Hanumanthu, V. S., & Armanios, M. Y. (2014) · CHEST Journal · doi:10.1378/chest.14-1947 · Cited by 185
Telomerase gene mutations are associated with cirrhosis formation
Hartmann, D., Srivastava, U., Thaler, M., Kleinhans, K. N., N'Kontchou, G., Scheffold, A., Bauer, K., Kratzer, R. F., Kloos, N., Katz, S.-F., et al. (2011) · Hepatology · doi:10.1002/hep.24217 · Cited by 173
Kropski, J. A., Pritchett, J. M., Zoz, D. F., Crossno, P. F., Markin, C. R., Garnett, E. T., Degryse, A. L., Mitchell, D. B., Polosukhin, V. V., Rickman, O. B., et al. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201406-1162oc · Cited by 184
“In summary, this report represents the most extensive histologic, radiographic, and molecular evaluation of a population at high risk for developing FIP and IPF performed to date.”
BackgroundInfluentialKadota, T., Fujita, Y., Yoshioka, Y., Araya, J., Kuwano, K., & Ochiya, T. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.11.005 · Cited by 179
Telomeropathies: An emerging spectrum disorder
Holohan, B., Wright, W. E., & Shay, J. W. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201401012 · Cited by 175
“Inherited mutations in TERC and TERT explain 8–20% of familial cases of IPF, as well as a small proportion of sporadic IPF cases (Tsakiri et al., 2007).”
Self-citationRole of Type II Pneumocyte Senescence in Radiation-Induced Lung Fibrosis
Citrin, D. E., Shankavaram, U. T., Horton, J. A., Shield, W. P., Zhao, S., Asano, H., White, A. O., Sowers, A. L., Thetford, A., & Chung, E. J. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt212 · Cited by 187
“Supporting the importance of the replicative potential of pneumocytes in pulmonary fibrosis, mutations of TERT (telomerase reverse transcriptase) and TERC (RNA component of telomerase) have been identified as causes of inherited idiopathic pulmonary fibrosis (33,34).”
BackgroundHill, C. N., Li, J., Liu, D., Conforti, F., Brereton, C. J., Yao, L., Zhou, Y., Alzetani, A., Chee, S., Marshall, B. G., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1820-x · Cited by 177
Niewisch, M. R., & Savage, S. A. (2019) · Expert Review of Hematology · doi:10.1080/17474086.2019.1662720 · Cited by 189
“in 2007 with the discovery of germline mutations in telomere biology genes as the cause of familial PF [128,129].”
BackgroundInfluentialTelomere Length and Use of Immunosuppressive Medications in Idiopathic Pulmonary Fibrosis
Newton, C. A., Zhang, D., Oldham, J. M., Kozlitina, J., Ma, S., Martínez, F. J., Raghu, G., Noth, I., & Garcia, C. K. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201809-1646oc · Cited by 181
“Rare variants in several of these genes have been found in adult patients with nonfamilial IPF (4, 10, 11).”
BackgroundSelf-citationAdvances in the understanding of dyskeratosis congenita
Walne, A. J., & Dokal, I. S. (2009) · British Journal of Haematology · doi:10.1111/j.1365-2141.2009.07598.x · Cited by 179
“Some patients with idiopathic pulmonary fibrosis have been shown to have mutations in either TERT or TERC (Armanios et al, 2007; Tsakiri et al, 2007).”
BackgroundNewton, C. A., Oldham, J. M., Ley, B., Anand, V. C., Adegunsoye, A., Liu, G. Y., Batra, K., Torrealba, J. R., Kozlitina, J., Glazer, C. S., et al. (2019) · European Respiratory Journal · doi:10.1183/13993003.01641-2018 · Cited by 180
Self-citationJiang, H., Schiffer, E., Song, Z., Wang, J., Zürbig, P., Thedieck, K., Moes, S., Bantel, H., Saal, N., Jantos, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801457105 · Cited by 169
Molecular biomarkers in idiopathic pulmonary fibrosis
Ley, B., Brown, K. K., & Collard, H. R. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00014.2014 · Cited by 176
Lung cancer in patients with idiopathic pulmonary fibrosis
Karampitsakos, Τ., Tzilas, V., Tringidou, R., Steiropoulos, P., Aidinis, V., Papiris, S. A., Bouros, D. E., & Τzouvelekis, Α. (2017) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2017.03.016 · Cited by 173
“Telomere length of peripheral blood leukocytes has been recently demonstrated to represent a strong predictor of IPF mortality, independent of demographic and functional prognosticators (78) (81, 82).”
BackgroundThe molecular genetics of the telomere biology disorders
Bertuch, A. A. (2015) · RNA Biology · doi:10.1080/15476286.2015.1094596 · Cited by 173
“The estimates vary, but up to 20 percent of IPF probands have a family history of IPF, with their pedigrees displaying a pattern consistent with autosomal dominant inheritance with incomplete penetrance.78 Mutations in TERT were the first to be identified in familial and some cases of sporadic IPF, linking a defect in…”
BackgroundApoptosis in lung injury and fibrosis
Drakopanagiotakis, F., Xifteri, A., Polychronopoulos, V., & Bouros, D. E. (2008) · European Respiratory Journal · doi:10.1183/09031936.00176807 · Cited by 168
Barkauskas, C. E., & Noble, P. W. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00321.2013 · Cited by 168
Blue Journal Conference. Aging and Susceptibility to Lung Disease
Thannickal, V. J., Murthy, M., Balch, W. E., Chandel, N. S., Meiners, S., Eickelberg, O., Selman, M., Pardo, A., White, E. S., Levy, B. D., et al. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201410-1876pp · Cited by 165
“patients with shortened telomeres are at increased risk of developing pulmonary fibrosis (25, 26) and telomere shortening has been noted in patients with emphysema”
BackgroundTelomere shortening and ageing
Jiang, H., Ju, Z., & Rudolph, K. L. (2007) · Zeitschrift für Gerontologie und Geriatrie · doi:10.1007/s00391-007-0480-0 · Cited by 165
“In addition, mutations in the catalytic subunit of telomerase (Tert) have been identified in different forms of anemia [36] and Tert mutations are also linked to the development of idiopathic pulmonary fibrosis in ca. 10% of the cases [37, 38 ].”
BackgroundCurrent status of genome-wide association studies in cancer
Chung, C. C., & Chanock, S. J. (2011) · Human Genetics · doi:10.1007/s00439-011-1030-9 · Cited by 166
A method for measuring the distribution of the shortest telomeres in cells and tissues
Lai, T., Zhang, N., Noh, J., Mender, I., Tedone, E., Huang, E. E., Wright, W. E., Danuser, G. M., & Shay, J. W. (2017) · Nature Communications · doi:10.1038/s41467-017-01291-z · Cited by 174
Self-citationRole of shelterin in cancer and aging
Martínez, P., & Blasco, M. A. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00596.x · Cited by 136
“Indeed, some diseases characterized by premature loss of tissue renewal and premature death, such as dyskeratosis congenita, as well as some cases of aplastic anemia and idiopathic pulmonary fibrosis, are linked to germline mutations in the Terc and Tert telomerase essential genes (Mitchell et al., 1999; Vulliamy et a…”
BackgroundLatella, G., Rogler, G., Bamias, G., Breynaert, C. M., Florholmen, J., Pellino, G., Reif, S. S., Speca, S., & Lawrance, I. C. (2014) · Journal of Crohn s and Colitis · doi:10.1016/j.crohns.2014.03.008 · Cited by 169
Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis
Kannengiesser, C., Borie, R., Ménard, C., Réocreux, M., Nitschké, P., Gazal, S., Mal, H., Taillé, C., Cadranel, J. L., Nunès, H., et al. (2015) · European Respiratory Journal · doi:10.1183/09031936.00040115 · Cited by 174
The genetics of dyskeratosis congenita
Mason, P. J., & Bessler, M. (2011) · Cancer Genetics · doi:10.1016/j.cancergen.2011.11.002 · Cited by 167
“At the same time a second group of investigators, using linkage studies on 2 large families with multiple cases of PF, mapped the responsible gene to interval 5p15(72).”
BackgroundTelomere-associated aging disorders
Opresko, P. L., & Shay, J. W. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.009 · Cited by 162
Self-citationHuman diseases of telomerase dysfunction: insights into tissue aging
Garcia, C. K., Wright, W. E., & Shay, J. W. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm644 · Cited by 161
“The missense mutations demonstrate a range of 30–100% wild-type telomerase activity in conventional rabbit reticulocyte in vitro assays (87).”
BackgroundMethodInfluentialSelf-citationGenetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis
Kropski, J. A., Lawson, W. E., Young, L. R., & Blackwell, T. S. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.010736 · Cited by 161
“Another group also identified TERT or TERC mutations in 7 of 44 FIP families, although in this cohort some family members had other features of DC (Tsakiri et al., 2007).”
BackgroundMaitra, M., Wang, Y., Gerard, R. D., Mendelson, C. R., & Garcia, C. K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.121467 · Cited by 159
Self-citationDyskeratosis congenita, stem cells and telomeres
Kirwan, M., & Dokal, I. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.01.010 · Cited by 180
“Heterozygous TERC and TERT mutations have also been implicated in cases of idiopathic pulmonary fibrosis (IPF) [24, 25], a chronic progressive lung disease with irreversible fibrosis leading to respiratory failure in most cases within five years [26].”
BackgroundInfluentialA Novel Dyskerin (DKC1) Mutation Is Associated With Familial Interstitial Pneumonia
Kropski, J. A., Mitchell, D. B., Markin, C. R., Polosukhin, V. V., Choi, L., Johnson, J. E., Lawson, W. E., Phillips, J. A., Cogan, J. D., Blackwell, T. S., et al. (2014) · CHEST Journal · doi:10.1378/chest.13-2224 · Cited by 155
Gerstberger, S. C., Hafner, M., Ascano, M., & Tuschl, T. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-1221-6_1 · Cited by 154
Hartmann, N., Reichwald, K., Lechel, A., Graf, M., Kirschner, J., Dorn, A., Tozzini, E. T., Wellner, J., Platzer, M., Rudolph, K. L., et al. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.01.003 · Cited by 154
“…several human syndromes such as dyskeratosis congenita, aplastic anemia and idiopathic pulmonary fibrosis that are caused by mutations in the telomerase genes and are characterised by increased shortening of telomeres with age (Vulliamy et al., 2004; Yamaguchi et al., 2005; Tsakiri et al., 2007).”
BackgroundGermline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer
Nathan, N., Giraud, V., Picard, C., Nunès, H., Moal, F., Copin, B., Galeron, L., Ligniville, A. D., Kuziner, N., Reynaud‐Gaubert, M., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw014 · Cited by 158
Schaetzlein, S., Nalapareddy, K., Ju, Z., Lechel, A., Stępczyńska, A., Lilli, D. R., Clark, A. B., Rudolph, C., Kühnel, F., Wei, K., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.029 · Cited by 146
Tejera, Á. M., d’Alcontres, M. S., Thanasoula, M., Marión, R. M., Martínez, P., Liao, C., Flores, J. M., Tarsounas, M., & Blasco, M. A. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.03.011 · Cited by 157
“Tsakiri et al., 2007.”
BackgroundKuwano, K., Araya, J., Hara, H., Minagawa, S., Takasaka, N., Ito, S., Kobayashi, K., & Nakayama, K. (2016) · Respiratory Investigation · doi:10.1016/j.resinv.2016.03.010 · Cited by 150
“[52] Tsakiri KD, Cronkhite JT, Kuan PJ, et al.”
BackgroundGenetics of leukocyte telomere length and its role in atherosclerosis
Aviv, A. (2012) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2011.05.001 · Cited by 143
It all comes together at the ends: Telomerase structure, function, and biogenesis
Podlevsky, J. D., & Chen, J. J. ‐. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.11.002 · Cited by 152
Unraveling the pathogenesis of Hoyeraal–Hreidarsson syndrome, a complex telomere biology disorder
Glousker, G., Touzot, F., Revy, P., Tzfati, Y., & Savage, S. A. (2015) · British Journal of Haematology · doi:10.1111/bjh.13442 · Cited by 149
“…(AR) mutations have been described in TERT, with diverse clinical presentations from pulmonary fibrosis and aplastic anaemia to DC and HH (Armanios et al, 2005; Vulliamy et al, 2005; Yamaguchi et al, 2005; Vulliamy et al, 2006; Marrone et al, 2007; Tsakiri et al, 2007; Basel-Vanagaite et al, 2008).”
BackgroundBorie, R., Kannengiesser, C., Hirschi, S., Pavec, J. L., Mal, H., Bergot, E., Jouneau, S., Naccache, J., Revy, P., Boutboul, D., et al. (2014) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2014.11.010 · Cited by 151
“transcriptase) and TR (encoding the telomerase RNA component), which are both required for normal telomerase activity [5].”
BackgroundEpigenetics of idiopathic pulmonary fibrosis
Yang, I. V., & Schwartz, D. A. (2014) · Translational research · doi:10.1016/j.trsl.2014.03.011 · Cited by 144
“Thus, we conducted a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication analyses in 876 cases and 1,890 controls [20] and confirmed association with TERT at 5p15, MUC5B at 11p15 and the…”
BackgroundInfluentialDyskeratosis congenita as a disorder of telomere maintenance
Nelson, N. D., & Bertuch, A. A. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.06.008 · Cited by 140
Strong, M. A., Vidal-Cardenas, S. L., Karim, B. O., Yu, H. M., Guo, N., & Greider, C. W. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05312-11 · Cited by 136
“Short telomeres are also associated with a broad spectrum of degenerative disorders that are linked to aging, including aplastic anemia, pulmonary fibrosis, liver disease, and others (1, 4, 5, 11, 41, 70, 78, 79).”
BackgroundDisayabutr, S., Kim, E. K., Cha, S.-I., Green, G., Naikawadi, R. P., Jones, K. D., Golden, J. A., Schroeder, A., Matthay, M. A., Kukreja, J., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0158367 · Cited by 136
“Recent reports have associated mutations in TERT or TERC [4, 29, 30] and the presence of short telomeres in type II AECs [4] to the development of IPF.”
Peljto, A. L., Selman, M., Kim, D. S., Murphy, E., Tucker, L., Pardo, A., Lee, J. S., Ji, W., Schwarz, M. I., Yang, I. V., et al. (2014) · CHEST Journal · doi:10.1378/chest.14-0867 · Cited by 142
From ARDS to pulmonary fibrosis: the next phase of the COVID-19 pandemic?
Michalski, J. E., Kurche, J. S., & Schwartz, D. A. (2021) · Translational research · doi:10.1016/j.trsl.2021.09.001 · Cited by 139
“Additionally, genetic variants in at least 5 telomere related genes which functionally shorten telomere length have been associated with increased risk of IPF.(96-103) Even without these telomere-shortening mutations, IPF patients have telomeres that are shorter than agematched controls.”
BackgroundNewton, C. A., Kozlitina, J., Lines, J. R., Kaza, V., Torres, F., & Garcia, C. K. (2017) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2017.02.005 · Cited by 132
Self-citationGenetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment
Kaur, A., Mathai, S. K., & Schwartz, D. A. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00154 · Cited by 132
“Am J Respir Crit Care Med (2008) 178(7):729–37.”
BackgroundInfluentialTelomere-mediated lung disease
Alder, J. K., & Armanios, M. (2022) · Physiological Reviews · doi:10.1152/physrev.00046.2021 · Cited by 130
Hepatopulmonary Syndrome Is a Frequent Cause of Dyspnea in the Short Telomere Disorders
Gorgy, A. I., Jonassaint, N. L., Stanley, S. E., Koteish, A. A., Dezern, A. E., Walter, J. E., Sopha, S. C., Hamilton, J. P., Hoover-Fong, J. E., Chen, A. R., et al. (2015) · CHEST Journal · doi:10.1378/chest.15-0825 · Cited by 132
European Respiratory Society statement on familial pulmonary fibrosis
Borie, R., Kannengiesser, C., Antoniou, K. M., Bonella, F., Crestani, B., Fabre, A., Froidure, A., Galvin, L., Griese, M., Grutters, J. C., et al. (2022) · European Respiratory Journal · doi:10.1183/13993003.01383-2022 · Cited by 136
Beginning at the ends: telomeres and human disease
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Comorbidities in idiopathic pulmonary fibrosis: an underestimated issue
Caminati, A., Lonati, C., Cassandro, R., Elia, D., Pelosi, G., Torre, O., Zompatori, M., Uslenghi, E., & Harari, S. A. (2019) · European Respiratory Review · doi:10.1183/16000617.0044-2019 · Cited by 134
The Role of Telomeres in Human Disease
Armanios, M. Y. (2022) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-010422-091101 · Cited by 126
“For example, approximately one-third of familial cases of pulmonary fibrosis (20% of idiopathic pulmonary fibrosis cases are familial) carry one of eight telomere-shortening mutations (7, 8, 19, 33, 39, 40, 71, 89, 91, 95) (Table 1).”
BackgroundIdiopathic Pulmonary Fibrosis: Update on Genetic Discoveries
Garcia, C. K. (2011) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201008-056ms · Cited by 131
“Cotranslation of different ratios of the V747fs and wildtype TERT protein did not negatively affect the activity of the wild-type protein, suggesting a mechanism of haploinsufficiency (25).”
BackgroundMethodSelf-citationMolecular Mechanisms in Progressive Idiopathic Pulmonary Fibrosis
Steele, M. P., & Schwartz, D. A. (2012) · Annual Review of Medicine · doi:10.1146/annurev-med-042711-142004 · Cited by 126
Progress in Understanding and Treating Idiopathic Pulmonary Fibrosis
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Dyskeratosis congenita: The diverse clinical presentation of mutations in the telomerase complex
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Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis
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“Many different molecular processes such as epithelial mesenchymal transition [14], apoptosis [15], endoplasmic reticulum stress [16], telomere shortening-associated senescence [17], and hypersecretion of MUC5B caused by a point mutation in the promoter region of the gene [18] are involved in the mechanisms of epitheli…”
Senotherapeutics: targeting senescence in idiopathic pulmonary fibrosis
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Revertant Somatic Mosaicism by Mitotic Recombination in Dyskeratosis Congenita
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“Mutations in hTERT or hTR underlie the inheritance in 8–15% of familial forms of pulmonary fibrosis and 1–3% of sporadic cases [12–15].”
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“The identification of major mutations in telomerase, which may cause diseases such as dyskeratosis congenita (1) and pulmonary fibrosis (2), has helped to explain the phenotypic manifestations of these monogenetic diseases in humans.”
Idiopathic Pulmonary Fibrosis: A Disorder of Epithelial Cell Dysfunction
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Short telomere length in IPF lung associates with fibrotic lesions and predicts survival
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“Additionally, literature postulated that shortened telomere length in blood is a risk factor for sporadic IPF and FIP-TERT subjects [6,7,11–13 To clinically target the potential pathogenic AT2 cells in fibrosis, it might be feasible in the near future to introduce AT2 cell transplantation.”
IPF: new insight on pathogenesis and treatment
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“Recently, the presence of heterozygous mutations in the telomerase reverse transcriptase (hTERT) and/or RNA component (hTR) genes encoding telomerase components have been reported in several families with IPF and in one patient with sporadic IPF (75, 119).”
BackgroundErratum: Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease
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Self-citationTissue remodelling in pulmonary fibrosis
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“In this regard, several cases of familial interstitial pneumonias, mostly IPF, with mutations in the telomerase genes, namely telomerase-reverse transcriptase (TERT) and telomerase RNA component (TERC; Armanios et al. 2007; Tsakiri et al. 2007) and other telomere-associated genes (e.”
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Variation at theTERTlocus and predisposition for cancer
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Biomarkers in idiopathic pulmonary fibrosis
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Cell senescence and fibrotic lung diseases
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Idiopathic Pulmonary Fibrosis: From Epithelial Injury to Biomarkers - Insights from the Bench Side
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Viral infection and aging as cofactors for the development of pulmonary fibrosis
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Chang, W., Wei, K., Jacobs, S. S., Upadhyay, D., Weill, D., & Rosen, G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025684 · Cited by 116
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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