GENETIC STUDIES OF ANEURYSMAL SUBARACHNOID HEMORRHAGE

中风是第三大死亡原因，也是成年人残疾的主要原因。 最近的研究强调了遗传因素在几种类型的中风病因学中的重要性。 特别是，遗传流行病学和分子遗传学研究支持遗传因素在家族性颅内动脉瘤（IA）发病机制中的重要性， 蛛网膜下腔出血（SAH）。 这个以患者为导向的项目的总体目标是促进对家族性IA和SAH的遗传因素的研究。 主要假设为 特定的突变或易感基因座有助于家族性IA和SAH的发展。 由于缺乏多个患有IA或SAH的患者的家庭，最初将使用候选基因方法。 基于弹性蛋白在血管完整性中的重要性，以及先前的研究显示IA和SAH患者中弹性蛋白、弹性蛋白酶和弹性蛋白酶抑制剂的改变，我们将关注弹性蛋白代谢相关的基因。 如果家庭资源充足， 一旦确定，将进行遗传连锁研究。 家族性IA/SAH的突变或遗传易感性位点的鉴定将极大地影响此类患者的护理，并有助于筛查和治疗有风险的无症状家庭成员。 该项目主要侧重于以患者为导向的研究。 主要研究者将参与IA/SAH家族的诊断和确定。 无症状风险 家庭成员将被告知需要使用非侵入性技术（如磁共振血管造影和CT血管造影）进行未破裂IA的筛查。 的 以实验室为基础的研究将集中于利用PCR、SSCP和DNA测序技术筛选候选基因。 本研究项目结合PI的背景和专业知识，为临床和遗传研究提供了广泛的以患者为导向的指导机会。

Stroke is the third leading cause of death and the leading cause of disability among adults. Recent studies have highlighted the importance of genetic factors in the etiology of several types of stroke. In particular, genetic epidemiologic and molecular genetic studies support the importance of genetic factors in the pathogenesis of familial intracranial aneurysms (IAs) and subarachnoid hemorrhage (SAH). The overall goal of this patient-oriented project is to advance the study of genetic factors responsible for familial IAs and SAH. The primary hypothesis is that specific mutations or susceptibility loci contribute to the development of familial IAs and SAH. Due to the paucity of families with multiple living affecteds having IAs or SAH, a candidate gene approach will be utilized initially. We will focus on genes involved in the metabolism of elastin, based on its importance in vascular integrity and prior studies showing altered elastin, elastase, and elastase inhibitors in patients with IAs and SAH. When adequate family resources are ascertained, genetic linkage studies will be performed. The identification of mutations or genetic susceptibility loci for familial IA/SAH will greatly influence the care of such patients as well as aid the screening and treatment of at-risk asymptomatic family members. This project has a major focus on patient-oriented research. The principal investigator will be involved in the diagnosis and ascertainment of families with IA/SAH. Asymptomatic at-risk family members will be counseled about the need to undergo screening for unruptured IAs using non-invasive techniques such as magnetic resonance angiography and CT angiography. The laboratory based research will focus on screening candidate genes using PCR, SSCP and DNA sequencing techniques. This research project combined with the PI's background and expertise provide a wide range of patient-oriented mentorship opportunities in clinical and genetic research.