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Single gene defect can cause stroke, other artery diseases
Date:5/1/2009

ic stroke, including Moyamoya disease, and 15 had more than one vascular disease.

In thoracic aortic disease, the wall of the aorta, the main blood vessel leading out of the heart, weakens and forms an aneurysm that can ultimately lead to an aortic dissection and death. Coronary artery disease, the most common type of heart disease, is the leading cause of death for both men and women in the United States. Stroke is the third leading cause of death in the country.

In the study, none of the family members without the ACTA2 defect had any vascular disease, helping to rule out other genetic or environmental causes. In four families, members younger than age 20 suffered a stroke and five strokes resulted from Moyamoya disease, a rare stroke disease in which the internal carotid arteries become occluded.

The main function of smooth muscle cells is to contract in response to the stretching from pulsing blood flow. Vascular pathology from mutant aortas and analysis of smooth muscle cells removed from patients and grown in the laboratory suggest that persons with ACTA2 have increased multiplication of smooth muscle cells that contribute to blocked or enlarged arteries, according to the study.

Milewicz and her team previously discovered the role of the mutated ACTA2; mutations in ACTA2 account for 14 percent of the inherited form of thoracic aortic aneurysms and dissections, making it the major gene identified for the condition.

During the research, Milewicz identified a large family with persistent livedo reticularis, a purplish mesh-like skin discoloration caused by the occlusion of arteries in the skin. This family also had a history of premature onset coronary artery disease and premature stroke without the risk factors know to cause these diseases (smoking, high cholesterol)

"Family members asked if it all could be related and I told them at the time that they just had really bad luck with several mutated genes," M
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Contact: Deborah Mann Lake
deborah.m.lake@uth.tmc.edu
713-500-3304
University of Texas Health Science Center at Houston
Source:Eurekalert  

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