Long QT Syndrome: Population, Genetic & Cardiac Studies

长 QT 综合征：人群、遗传

• 批准号: 6782591
• 负责人: ARTHUR J. MOSS
• 金额: $ 56.52万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-02-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6782591
• 关键词: autosomal dominant trait; cardiovascular disorder epidemiology; clinical research; comorbidity; congenital heart disorder; disease /disorder proneness /risk; electrocardiography; family genetics; gene frequency; gene mutation; genetic disorder diagnosis; genotype; heart disorder diagnosis; human population genetics; human population study; human subject; linkage mapping; long QT syndrome; longitudinal human study; phenotype; prognosis; statistics /biometry; sudden cardiac death

DESCRIPTION (provided by applicant): The proposed research is a multidisciplinary, multicenter, collaborative study to continue the investigation of the clinical, cardiac, and genetic aspects of the Long QT Syndrome (LQTS) - a heritable channelopathy with delayed ventricular repolarization and episodic malignant arrhythmias manifest by syncope and sudden death. Presently, over 300 mutations on 6 ion-channel genes (KCNQ1, HERG, SCNhA, minK, MIRP1, and KCNJ2) have been identified in LQTS. The five-year research activity will: 1) continue to upgrade, expand, and collect clinical and genetic data on 900 active LQTS families (5,508 active family members) currently enrolled in the LQTS Registry; 2) develop a multivariate prognostic risk-scoring system using different time origins (from birth, and from age 10, 20, and 40 years); 3) evaluate the effectiveness and limitations of LQTS therapies; and 4) expand investigations into LQTS genotype-phenotype relationships. Functionally, the grant has four sections: a clinical section involving six clinical centers that have enrolled and are actively following the LQTS families in the Registry; a genotype section involving four experienced molecular genetic laboratories; a biostatistical section that will provide expertise in study design and statistical data analyses; and a central coordination and data center that will provide data management and coordination of the various components of the program. This integrated research program offers a substantial prospect of: 1) improving the diagnosis, management, and treatment of individuals affected with LQTS; and 2) providing a fundamental understanding of the molecular basis of repolarization-related cardiac arrhythmias in patients with a broad spectrum of cardiac disorders.

描述（由申请人提供）：拟议的研究是一项多学科、多中心、协作研究，旨在继续研究长 QT 综合征 (LQTS) 的临床、心脏和遗传方面，LQTS 是一种伴有心室复极延迟和阵发性恶性的遗传性离子通道病。心律失常表现为晕厥和猝死。目前，LQTS 中已发现 6 个离子通道基因（KCNQ1、HERG、SCNhA、minK、MIRP1 和 KCNJ2）的 300 多个突变。这项为期五年的研究活动将：1）继续升级、扩展和收集目前在 LQTS 登记处登记的 900 个活跃 LQTS 家庭（5,508 名活跃家庭成员）的临床和遗传数据； 2) 开发一个使用不同时间起点（从出生开始，以及从10岁、20岁和40岁开始）的多变量预后风险评分系统； 3）评估LQTS疗法的有效性和局限性； 4) 扩大对 LQTS 基因型-表型关系的研究。从功能上讲，该补助金分为四个部分：临床部分，涉及六个临床中心，这些中心已注册并积极跟踪注册中的 LQTS 家庭；基因型部分涉及四个经验丰富的分子遗传学实验室；生物统计部分将提供研究设计和统计数据分析方面的专业知识；中央协调和数据中心将为该计划的各个组成部分提供数据管理和协调。该综合研究项目提供了以下重大前景：1）改善 LQTS 患者的诊断、管理和治疗； 2) 提供对患有广泛心脏疾病的患者复极相关心律失常的分子基础的基本了解。