Multidisciplinary Study of Right Ventricular Dysplasia

右心室发育不良的多学科研究

• 批准号: 6644223
• 负责人: FRANK I MARCUS
• 金额: $ 54.47万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6644223
• 关键词: arrhythmia; cooperative study; diagnosis design /evaluation; family genetics; gene expression; gene mutation; genetic mapping; genetic susceptibility; heart disorder diagnosis; heart function; heart ventricle; human subject; longitudinal human study; pathologic process; patient /disease registry; patient oriented research

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.

描述（由申请人提供）： 此应用程序是一个群集提案的一部分， 组件：Frank Marcus博士的应用程序，描述了 科学计划，杰弗里·托宾博士的应用程序描述了 该研究的遗传分析以及Wojciech Zareba博士的提议 描述协调和数据中心的组织和运作 (CDC)为了研究拟议的五年研究计划是一个多学科的， 多中心，合作研究，调查心脏， 致心律失常性右心室发育不良的临床和遗传方面 （ARVD），一种进行性疾病，主要影响右侧， 引起室性心律失常。在许多患者中， 家族的ARVD可能占意外猝死的5% 65岁以下，运动猝死占3-4%。可以有 很难确定地诊断这种疾病， 关于发病机制、自然史和治疗的信息不完整 患者和受影响的成员。的总体目标 右室发育不良的多学科研究是为了表征 致心律失常性右心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 登记入组ARVD患者及其家庭成员，基于 标准化诊断测试标准，在前瞻性纵向随访中 研究; 2）通过鉴定ARVD的遗传背景， 与该疾病相关的染色体基因座和特定基因突变; 3)以确定基因型对临床病程的影响， ARVD患者，并探索表型-基因型相关性， 有助于改善诊断、风险分层和治疗;以及4） 开发定量方法评估右心室功能， 提高ARVD诊断的特异性和敏感性。这一综合 研究补助金提案提供了扩大基金的巨大前景， 有关ARVD和相关基因定位的临床知识 治疗这种疾病