DALLAS July 17, 2005 By studying five generations of a Dallas family, UT Southwestern Medical Center researchers have discovered that a mutation in a key gene causes aortic valve disease, a common heart birth defect as well as a major contributor to adult heart disease.
In the study, available in the online edition of the journal Nature, researchers scanned the DNA of 11 members of a family that was affected with aortic heart disease. The patients ranged from children with severe narrowing of the aortic valve to 50- and 60-year-olds who had such severe calcium buildup on their heart valves that they required replacement valves.
The UT Southwestern researchers found that all the relatives with some manifestation of aortic valve disease had a mutation in a gene called NOTCH1.
A second, smaller family in San Diego afflicted with the heart disorder also had members with a second mutation in the same gene, providing convincing evidence that the researchers had found the genetic link to aortic heart disease, said Dr. Vidu Garg, assistant professor of pediatrics and molecular biology and lead author of the study.
"Mutations in NOTCH1 cause an early developmental defect in the aortic valve," Dr. Garg said.
The aortic valve is located between the left ventricle, or lower chamber of the heart, and the largest artery, the aorta. The left ventricle pumps oxygen-rich blood into the aorta, which carries blood to the brain and the rest of the body.
The normal aortic valve is made up of three "leaflets," flaps of tissue that open and close to allow blood flow through the valve in only one direction. About 1 percent to 2 percent of the world's population is born with only two valve leaflets, a defect called bicuspid aortic valve. The condition predisposes individuals to aortic valve stenosis, a condition that severely narrows the passage for blood to exit the heart, and in many cases, requires surgery at birth.
The narrowing of the valve can be sPage: 1 2 3 Related biology news :1
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