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The Daniel and Joan Beren
Pennsylvania Idiopathic Pulmonary Fibrosis
State Registry

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New England Journal of Medicine


N. Engl J Med. 2007 Mar 29;356(13):1317-26.

Telemerase mutations in families with Idiopathic Pulmonary Fibrosis.

Armanior MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE, Xie M, Vulto I, Phillips JA, 3rd, Lansdorp PM, Greider CW, Loyd JE (2007)

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.



N Engl J Med. 2007 Mar 29;356(13):1370-2.

Idiopathic pulmonary fibrosis--new insights

Verma S, Slutsky, AS

Summary: Death occurred about three months and a half after the onset of the acute disease and the lung was two thirds of the normal size, grayish in color, and hard as cartilage. Microscopically these areas showed advanced fibrotic changes and great thickening of the alveolar walls." Thus did Sir William Osler describe, in 1892, a case of idiopathic pulmonary fibrosis1 — an unrelenting and progressive disease that afflicts more than 5 million patients worldwide. The number of patients who receive this diagnosis has doubled within the past decade, and yet there is no effective treatment. The overall prognosis is dismal, with a median survival of 3 to 5 years after diagnosis.2 Insights into the molecular mechanism of the disease, such as those provided by Armanios et al.3 in this issue of the Journal and Wang et al.4 in a recent report, are therefore especially valuable.