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Scientists identify gene that causes fatal lung disease

Doctors and researchers at Vanderbilt University Medical Center have identified a gene that causes Primary Pulmonary Hypertension (PPH), high blood pressure in the lungs. Without treatment, the disease is considered fatal.

VUMC researchers have determined that the gene involved is Bone Morphogenic Protein Receptor Two (BMPR2). When mutated, the gene causes cells to grow and clog the inside of blood vessels in the lungs, similar to clogged arteries in the heart.

"It's in the Transforming Growth Factor Beta (TGFb) family, which is a large family of different proteins that regulate cell growth and proliferation," said Dr. James E. Loyd, professor of medicine and one of the researchers.

"TGFb is a growth suppressor gene so this gene, BMPR2, normally prevents the cells from growing. When it mutates or is defective, the suppressor is stopped and it allows the cells to grow unregulated and they ultimately block the blood vessels.

"This is the first report of the gene and what it does. Now, for the first time, we know that there is a specific genetic defect of a particular receptor that is highly associated with the disease and must be the root cause of PPH."

Their research is reported in the September issue of Nature Genetics. Loyd was joined in this research by molecular biologist Kirk B. Lane, Ph.D., assistant professor in Medicine, the first to select BMPR2 as a candidate gene after reviewing the hundreds of genes which were known to reside in the region of chromosome 2q linked to PPH. Lane recognized that BMPR2 is a member of the TGFb family.

The first mutation of BMPR2 was demonstrated by DNA fingerprinting in the labs of Dr. John A. Phillips III, David T. Karzon Chair in Pediatrics. Other workers who participated in the PPH studies in Lane's labs were Dr. Radhika Gaddipati and upcoming medical student Emily Loyd, in addition to Melissa Prince in Phillips' lab. Also involved in the research were Dr. John H. Newman, Elsa S.
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Contact: John Howser
john.howser@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
25-Jul-2000


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