EXTRACELLUAR MATRIX GENE MUTATIONS IN AORTIC ANEURYSMS

这项建议的目的是开始定义遗传病的基础 家族性主动脉瘤。 主动脉瘤是一种比较常见的疾病，在老年人和 环境因素和遗传因素在该病的发病机制中都起重要作用。 这种病。从几个实验室最近的工作来看，包括 这项提案中提供的初步数据表明， III型胶原是一种丰富的血管基质蛋白，有助于 发生主动脉瘤的遗传易感性。 晚期红斑狼疮患者III型胶原基因突变的特征 成人发病的动脉瘤将首次提供机会， 评估突变的特定性质是否会影响 疾病的表型严重程度。此外，新的证据是 该提案证明了另一个基因的突变 血管基质蛋白，弹性蛋白，是导致单基因疾病的原因。 以血管破裂为特征的。此应用程序还打算搜索 主动脉瘤患者的弹性蛋白突变。 除了更好地了解主动脉瘤的病因外， 这项研究希望促进先兆遗传的可能性 早期诊断和手术治疗的疾病的风险分析 干预可以带来极好的长期存活率。

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.