Adult-onset pulmonary fibrosis caused by mutations in telomerase

Kalliopi D. Tsakiri, Jennifer T. Cronkhite, Phillip J. Kuan, Chao Xing, Ganesh Raghu, Jonathan C. Weissler, Randall L. Rosenblatt, Jerry W. Shay, Christine Kim Garcia

Research output: Contribution to journalArticlepeer-review

510 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7552-7557
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - May 1 2007


  • Aging
  • Genetics
  • Idiopathic pulmonary fibrosis
  • Telomeres

ASJC Scopus subject areas

  • General


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