EXTRACELLUAR MATRIX GENE MUTATIONS IN AORTIC ANEURYSMS

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The aim of this proposal is to begin to define the genetic basis of familial aortic aneurysms. Aortic aneurysms are a relatively common disorder amongst the elderly and both environmental and genetic factors are important in the pathogenesis of this disease. From recent work in several laboratories, including preliminary data presented in this proposal, it's clear that mutations in type III collagen, an abundant vascular matrix protein, contribute towards a genetic predisposition to the development of aortic aneurysms. The characterization of type III collagen mutations in patients with late adult onset aneurysms will provide for the first time, the opportunity to evaluate whether the specific nature of the mutation will influence the phenotypic severity of the disorder. In addition, new evidence is presented in the proposal that demonstrates that mutations in another vascular matrix protein, elastin, are responsible for a monogenic disease characterized by vascular rupture. This application also intends to search for elastin mutations in patients with aortic aneurysms. In addition to a better understanding of the etiology of aortic aneurysms, this study hopes to facilitate the possibility of pre-symptomatic genetic risks analysis in a disease in which early diagnosis and surgical intervention can result in excellent long term survival.