Genetics may underlie some artery ruptures.

Genetics may underlie some artery ruptures

Genetic tests of a Texas family with a marked vulnerability to aortic aneurysms--silent and sometimes fatal weakenings in the walls of the main artery leading from the heart--show that many members inherited a faulty gene, report researchers at Thomas Jefferson University in Philadelphia. "Our study proves for the first time that there is a genetic cause for aortic aneurysms," asserts study leader Darwin J. Prockop.

He and his colleagues have also developed a simple saliva test that offers hope for identifying others who carry aneurysm-associated genetic defects, perhaps in time to prevent a catastrophic blowout of the aorta wall.

The researchers initially focused their investigation on an apparently healthy 37-year-old woman, Michele Hegler, whose mother, aunt and 15-year-old cousing had died of aortic aneurysms. While analyzing DNA from Hegler's skin cells, the team homed in on the gene coding for collagen III--the tough, fibrous protein that gives aortic walls their strength. The analysis, described in the November JOURNAL OF CLINICAL INVESTICATION, revealed that the genetic instructions for producing collagen III contained a mutation resulting in the substitution of just one improper amino acid.

Prockop and his co-workers then examined aortic tissues that had been preserved after the death of Hegler's mother and aunt. DNA analysis confirmed that these contained the same flawed collage III gene. This genetic error, though tiny, appears to result in flimsy, rupture-prone aorta walls, the researchers say. They went on to develop a saliva test that identified the defect in several other family members, including Hegler's teenage son and daughter.

Aneurysms might result from any of a variety of mutations in the collagen III gene or in other genes that code for proteins used in constructing the aorta wall, Prockop suggests. In collaboration with other scientists, including vascular surgeon R. Clement Darling at the Harvard Medical School in Boston, Prockop's team is now studying 410 people with a family history of aortic aneurysm to see whether they carry such mutations.

If that study similarly turns up mutations responsible for weak aortas, clinicians might one day find it useful to screen relatives of aneurysm victims for signs of a genetic predisposition to this life-threatening condition, Prockop says.

Identifying high-risk individuals might enable physicians to stave off aneurysms with preventive treatment such as beta-blocker drugs that reduce the pounding pressure in blood vessels, he says. In addition, these people could undergo periodic ultrasound examinations to detect early signs of balloon-like aortic swellings. Darling predicts that some patients might opt for elective surgery to patch the damaged aorta wall rather than wait for the balloon to burst.