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Rare mutations linked with catastrophic aortic aneurysms

2010-11-19
(Press-News.org) TAAD causes thousands of deaths in the United States each year. Although timely surgical repair of aneurysms can prevent death, thoracic aneurysms are often asymptomatic until dissection (tearing of the vessel wall), and there are few recognized risk factors that can be used for screening. "Prospective identification of patients at risk for TAAD using a genetic strategy will be critical to prevent sudden deaths from this treatable disease," explains senior study author Dr. John W. Belmont from Baylor College of Medicine.

To begin to unravel the genetic origins of TAAD, lead author Dr. Siddharth Prakash and colleagues at Baylor and Dr. Dianna Milewicz and colleagues at the University of Texas Health Science Center in Houston performed a genome-wide analysis of hundreds of sporadic TAAD cases. The researchers identified 47 copy-number variant (CNV) regions in the TAAD samples when compared with control samples. A CNV is an excess or absence in copies of a particular gene. Previous research has demonstrated that CNVs are linked with many different human diseases.

Specifically, Dr. Prakash and colleagues found that genes within the TAAD CNVs regulate the ability of smooth muscle to firmly adhere within the vessel walls and to contract as the aorta expands and recoils. Importantly, the mutations were linked with molecules whose disruption has been shown to cause inherited TAAD. "Our observations provide strong support for the involvement of multiple rare CNVs that disrupt smooth muscle adhesion or contraction and contribute to both sporadic and familial TAAD. In addition, our findings have implications for other adult-onset cardiovascular disorders," concludes Dr. Belmont.

### The primary author for this research is John W. Belmont, Baylor College of Medicine

The first author for this research is Siddharth K. Prakash, Baylor College of Medicine


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[Press-News.org] Rare mutations linked with catastrophic aortic aneurysms