EXTRACELLUAR MATRIX GENE MUTATIONS IN AORTIC ANEURYSMS

该提案的目的是开始确定 家族性主动脉瘤 主动脉瘤是老年人中相对常见的疾病， 环境和遗传因素在发病机制中都很重要。 这种疾病。 从几个实验室最近的工作，包括 根据这项提案中提出的初步数据，很明显， III型胶原是一种丰富的血管基质蛋白， 一种易患主动脉瘤的遗传倾向 晚期乳腺癌患者III型胶原基因突变的特征 成人发作的动脉瘤将首次提供机会， 评估突变的具体性质是否会影响 疾病的表型严重程度。 此外，新的证据显示， 在提案中提出，证明另一个基因的突变 血管基质蛋白，弹性蛋白，是单基因疾病的原因 以血管破裂为特征。 该应用程序还打算搜索 在主动脉瘤患者中进行弹性蛋白突变的研究。 除了更好地了解主动脉瘤的病因外， 这项研究希望促进症状前遗传的可能性， 早期诊断和手术治疗的疾病的风险分析 干预可以导致极好长期存活。

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.