Life-threatening Gene Defect Located - Drug Discovery and Development

A research team led by scientists at The University of Texas Medical School at Houston has identified a defective gene that affects vascular smooth-muscle cells in people who suffer from hereditary thoracic aortic disease, which can kill victims with little warning in the prime of their lives. The study, “Mutations in Smooth Muscle Alpha-Actin (ACTA2) Lead to Thoracic Aortic Aneurysms and Dissections,” appears in Nature Genetics.

Research on 14 families with 93 members from across the United States, along with Europe and Australia, led the team to a mutation in the smooth muscle cell alpha-actin (ACTA2), which affects muscular contractions in other blood vessels and the aorta. The wall of the aorta, the main blood vessel leading out of the heart, weakens and then enlarges, forming an aneurysm and ultimately leading to an aortic dissection, which often causes sudden death.

“Our results suggest that contraction of the smooth muscle cells in the aorta is important in keeping it healthy and preventing the disease,” said the study’s senior author, Dianna M. Milewicz, M.D., Ph.D., professor and director of the Division of Medical Genetics at the UT Medical School. “This information provides insight into the cause of this condition and helps us understand, for the first time, the pathology of the aortic wall degeneration.”

Milewicz said that mutations in ACTA2 account for 14 percent of the inherited form of thoracic aortic aneurysms and dissections, making it the major gene identified for this condition.

Release date: November 11, 2007
Source: University of Texas Medical School at Houston