Telomerase mutations in families with idiopathic pulmonary fibrosis

Mary Y. Armanios, Julian Chen, Joy D. Cogan, Jonathan K. Alder, Roxann G. Ingersoll, Cheryl Markin, William E. Lawson, Mingyi Xie, Irma Vulto, John A. Phillips, Peter M. Lansdorp, Carol W. Greider, James E. Loyd

Research output: Contribution to journalArticle

737 Citations (Scopus)

Abstract

BACKGROUND: Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering of the disease are unknown. Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia and pulmonary fibrosis. METHODS: To test the hypothesis that familial idiopathic pulmonary fibrosis may be caused by short telomeres, we screened 73 probands from the Vanderbilt Familial Pulmonary Fibrosis Registry for mutations in hTERT and hTR. RESULTS: Six probands (8%) had heterozygous mutations in hTERT or hTR; mutant telomerase resulted in short telomeres. Asymptomatic subjects with mutant telomerase also had short telomeres, suggesting that they may be at risk for the disease. We did not identify any of the classic features of dyskeratosis congenita in five of the six families. CONCLUSIONS: Mutations in the genes encoding telomerase components can appear as familial idiopathic pulmonary fibrosis. Our findings support the idea that pathways leading to telomere shortening are involved in the pathogenesis of this disease.

Original languageEnglish (US)
Pages (from-to)1317-1326
Number of pages10
JournalNew England Journal of Medicine
Volume356
Issue number13
DOIs
StatePublished - Mar 29 2007

Fingerprint

Idiopathic Pulmonary Fibrosis
Telomerase
Telomere
Mutation
Pulmonary Fibrosis
Dyskeratosis Congenita
Telomere Shortening
Premature Mortality
Germ-Line Mutation
Aplastic Anemia
Genes
Cluster Analysis
Registries

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Armanios, M. Y., Chen, J., Cogan, J. D., Alder, J. K., Ingersoll, R. G., Markin, C., ... Loyd, J. E. (2007). Telomerase mutations in families with idiopathic pulmonary fibrosis. New England Journal of Medicine, 356(13), 1317-1326. https://doi.org/10.1056/NEJMoa066157

Telomerase mutations in families with idiopathic pulmonary fibrosis. / Armanios, Mary Y.; Chen, Julian; Cogan, Joy D.; Alder, Jonathan K.; Ingersoll, Roxann G.; Markin, Cheryl; Lawson, William E.; Xie, Mingyi; Vulto, Irma; Phillips, John A.; Lansdorp, Peter M.; Greider, Carol W.; Loyd, James E.

In: New England Journal of Medicine, Vol. 356, No. 13, 29.03.2007, p. 1317-1326.

Research output: Contribution to journalArticle

Armanios, MY, Chen, J, Cogan, JD, Alder, JK, Ingersoll, RG, Markin, C, Lawson, WE, Xie, M, Vulto, I, Phillips, JA, Lansdorp, PM, Greider, CW & Loyd, JE 2007, 'Telomerase mutations in families with idiopathic pulmonary fibrosis', New England Journal of Medicine, vol. 356, no. 13, pp. 1317-1326. https://doi.org/10.1056/NEJMoa066157
Armanios MY, Chen J, Cogan JD, Alder JK, Ingersoll RG, Markin C et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. New England Journal of Medicine. 2007 Mar 29;356(13):1317-1326. https://doi.org/10.1056/NEJMoa066157
Armanios, Mary Y. ; Chen, Julian ; Cogan, Joy D. ; Alder, Jonathan K. ; Ingersoll, Roxann G. ; Markin, Cheryl ; Lawson, William E. ; Xie, Mingyi ; Vulto, Irma ; Phillips, John A. ; Lansdorp, Peter M. ; Greider, Carol W. ; Loyd, James E. / Telomerase mutations in families with idiopathic pulmonary fibrosis. In: New England Journal of Medicine. 2007 ; Vol. 356, No. 13. pp. 1317-1326.
@article{b1f4a2b6166f453aac8bde23d98e1633,
title = "Telomerase mutations in families with idiopathic pulmonary fibrosis",
abstract = "BACKGROUND: Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering of the disease are unknown. Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia and pulmonary fibrosis. METHODS: To test the hypothesis that familial idiopathic pulmonary fibrosis may be caused by short telomeres, we screened 73 probands from the Vanderbilt Familial Pulmonary Fibrosis Registry for mutations in hTERT and hTR. RESULTS: Six probands (8{\%}) had heterozygous mutations in hTERT or hTR; mutant telomerase resulted in short telomeres. Asymptomatic subjects with mutant telomerase also had short telomeres, suggesting that they may be at risk for the disease. We did not identify any of the classic features of dyskeratosis congenita in five of the six families. CONCLUSIONS: Mutations in the genes encoding telomerase components can appear as familial idiopathic pulmonary fibrosis. Our findings support the idea that pathways leading to telomere shortening are involved in the pathogenesis of this disease.",
author = "Armanios, {Mary Y.} and Julian Chen and Cogan, {Joy D.} and Alder, {Jonathan K.} and Ingersoll, {Roxann G.} and Cheryl Markin and Lawson, {William E.} and Mingyi Xie and Irma Vulto and Phillips, {John A.} and Lansdorp, {Peter M.} and Greider, {Carol W.} and Loyd, {James E.}",
year = "2007",
month = "3",
day = "29",
doi = "10.1056/NEJMoa066157",
language = "English (US)",
volume = "356",
pages = "1317--1326",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "13",

}

TY - JOUR

T1 - Telomerase mutations in families with idiopathic pulmonary fibrosis

AU - Armanios, Mary Y.

AU - Chen, Julian

AU - Cogan, Joy D.

AU - Alder, Jonathan K.

AU - Ingersoll, Roxann G.

AU - Markin, Cheryl

AU - Lawson, William E.

AU - Xie, Mingyi

AU - Vulto, Irma

AU - Phillips, John A.

AU - Lansdorp, Peter M.

AU - Greider, Carol W.

AU - Loyd, James E.

PY - 2007/3/29

Y1 - 2007/3/29

N2 - BACKGROUND: Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering of the disease are unknown. Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia and pulmonary fibrosis. METHODS: To test the hypothesis that familial idiopathic pulmonary fibrosis may be caused by short telomeres, we screened 73 probands from the Vanderbilt Familial Pulmonary Fibrosis Registry for mutations in hTERT and hTR. RESULTS: Six probands (8%) had heterozygous mutations in hTERT or hTR; mutant telomerase resulted in short telomeres. Asymptomatic subjects with mutant telomerase also had short telomeres, suggesting that they may be at risk for the disease. We did not identify any of the classic features of dyskeratosis congenita in five of the six families. CONCLUSIONS: Mutations in the genes encoding telomerase components can appear as familial idiopathic pulmonary fibrosis. Our findings support the idea that pathways leading to telomere shortening are involved in the pathogenesis of this disease.

AB - BACKGROUND: Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering of the disease are unknown. Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia and pulmonary fibrosis. METHODS: To test the hypothesis that familial idiopathic pulmonary fibrosis may be caused by short telomeres, we screened 73 probands from the Vanderbilt Familial Pulmonary Fibrosis Registry for mutations in hTERT and hTR. RESULTS: Six probands (8%) had heterozygous mutations in hTERT or hTR; mutant telomerase resulted in short telomeres. Asymptomatic subjects with mutant telomerase also had short telomeres, suggesting that they may be at risk for the disease. We did not identify any of the classic features of dyskeratosis congenita in five of the six families. CONCLUSIONS: Mutations in the genes encoding telomerase components can appear as familial idiopathic pulmonary fibrosis. Our findings support the idea that pathways leading to telomere shortening are involved in the pathogenesis of this disease.

UR - http://www.scopus.com/inward/record.url?scp=34047188508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047188508&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa066157

DO - 10.1056/NEJMoa066157

M3 - Article

VL - 356

SP - 1317

EP - 1326

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 13

ER -