Multidisciplinary Study of Right Ventricular Dysplasia

描述(由申请人提供)： 此应用程序是由三个方案组成的集群方案的一部分 组件：Frank Marcus博士的应用程序描述了整个 科学计划，杰弗里·托宾博士的一份申请描述了 这项研究的遗传分析，以及Wojciech Zareba博士的建议 描述协调和数据中心的组织和运营 (CDC)用于这项研究。拟议的五年计划是一个多学科的研究计划， 多中心，合作研究，以调查心脏， 致心律失常性右室发育不良的临床和遗传学特点 (ARVD)，一种进行性疾病，主要影响右侧 并导致室性心律失常。在许多患者中，这种疾病是 有家族性。ARVD可能导致高达5%的意外猝死 65岁以下和3-4%的人在运动期间猝死。可能会有 要确定诊断这种疾病相当困难，而且还有 关于发病机制、自然病史和治疗方法的信息不完整 患者和受影响成员的名单。《公约》的总体目标 右室发育不良的多学科研究 致心律失常性右室发育不良的遗传和临床特征 (ARVD)。具体目标是：1)建立北美ARVD 登记ARVD患者及其家庭成员，基于 前瞻性纵向随访中的标准化诊断测试标准 研究：2)确定ARVD的遗传背景 与该疾病相关的染色体位点和特定基因突变； 3)确定基因分型对临床病程的影响。 ARVD患者，并探索表型-基因关联将 有助于改进诊断、风险分层和治疗；以及4) 开发定量方法来评估右心功能，以便 提高ARVD诊断的特异性和敏感性。这一集成 研究资助建议提供了一个扩大基金的巨大前景 有关ARVD的临床知识和基因定位(S)负责 来治疗这种疾病。

DESCRIPTION (provided by applicant): This application is part of a clustered proposal consisting of three components: an application by Dr. Frank Marcus describing the overall scientific program, an application by Dr. Jeffrey Towbin describing the genetic analyses for the study, and a proposal by Dr. Wojciech Zareba describing the organization and operation of the Coordination and Data Center (CDC) for the study. The proposed five-year research plan is a multi-disciplinary, multicenter, collaborative study to investigate the cardiac, clinical, and genetic aspects of arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias. In many patients the disease is familial. ARVD may account for as many as 5% of unexpected sudden deaths under the age of 65 and 3-4% of sudden death during sports. There can be considerable difficulty in diagnosing this disease with certainty, and there is incomplete information on the pathogenesis, natural history, and treatment of the patients and affected members. The overall objective of the Multidisciplinary Study of Right Ventricular Dysplasia is to characterize the genetic and clinical features of arrhythmogenic right ventricular dysplasia (ARVD). The specific aims are: 1) to establish a North American ARVD Registry enrolling ARVD patients and their family members, based on standardized diagnostic test criteria, in a prospective longitudinal follow-up study; 2) to determine the genetic background of ARVD by identifying chromosomal loci and specific gene mutations associated with this disorder; 3) to determine the influence of the genotype on the clinical course of patients with ARVD and explore phenotype-genotype associations that will contribute to improved diagnosis, risk stratification, and therapy; and 4) to develop quantitative methods to assess right ventricular function in order to enhance the specificity and sensitivity of ARVD diagnosis. This integrated research grant proposal offers a substantial prospect of expanding the fund of clinical knowledge regarding ARVD and of localizing the gene(s) responsible for this disorder.