New England Journal of Medicine
N. Engl J Med. 2007 Mar 29;356(13):1317-26.
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)
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
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.
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N Engl J Med. 2007 Mar 29;356(13):1370-2.
Verma S, Slutsky, AS
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.
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