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UT Southwestern researchers identify gene linked to inherited form of fatal lung disease
Date:12/19/2008

normally responsible for producing the telomerase enzyme, which elongates the lengths of DNA at the ends of chromosomes, called telomeres. In normal cells, telomeres shorten each time the cell divides. When they reach a certain length, the cell stops dividing. In most cancerous cells, telomeres don't shorten during cell division, allowing the cells to remain effectively immortal. Mutations in either of these two genes can be found in almost 15 percent of those with familial IPF. Up to 40 percent have short telomere lengths and evidence of telomerase dysfunction.

"But we were still left with a big question mark," Dr. Garcia said. "What about the rest of the families that have normal telomere lengths? What was causing their lung disease?"

In the current study, Dr. Garcia and her team focused on families that did not have TERC or TERT mutations. By using a genomic linkage approach a technique that scans the entire human genome for regions of DNA that are shared in common by all the individuals with the disease they were led to mutations in a gene called SFTPA2. The protein produced by this gene, surfactant protein A2, is found in the fluid of the lungs and helps protect the organ from invading pathogens.

Many of the individuals in this family who carried this mutation had not only IPF but also lung cancer, especially adenocarcinoma, with features of bronchioloalveolar cell carcinoma. It is known that people with IPF have a higher risk for developing lung cancer, and Dr. Garcia suspects that mutations in the SFTPA2 gene are associated with both IPF and lung cancer. Another family harboring a different mutation in the SFTPA2 gene also had members that exhibited IPF and lung cancer.

Dr. Garcia and her team are now working on molecular studies in cells to determine why these gene mutations put patients at risk for either of these diseases. They are also working to develop an animal model in order to determine the specific effects of
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Contact: Connie Piloto
connie.piloto@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

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UT Southwestern researchers identify gene linked to inherited form of fatal lung disease
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