Long QT Syndrome: Population, Genetic & Cardiac Studies

描述（由申请人提供）：拟议的研究是一项多学科、多中心、合作研究，旨在继续调查长QT综合征（LQTS）的临床、心脏和遗传方面的问题。LQTS是一种遗传性通道病，伴延迟心室复极和发作性恶性心律失常，表现为晕厥和猝死。目前，已经在LQTS中发现了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家族（5508名活跃家庭成员）的临床和遗传数据；2)建立一个多变量预后风险评分系统，使用不同的时间起点（从出生开始，从10岁、20岁和40岁开始）；3)评价LQTS疗法的有效性和局限性；4)扩大LQTS基因型-表型关系的研究。从功能上讲，该赠款分为四个部分：一个临床部分涉及六个临床中心，这些中心已注册并正在积极跟踪登记处的LQTS家庭；由四个经验丰富的分子遗传学实验室组成的基因型组；生物统计学部分，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提供数据管理和协调项目的各个组成部分。这个综合研究项目提供了大量的前景：1)改善LQTS患者的诊断、管理和治疗；2)对广谱心脏疾病患者复极相关心律失常的分子基础有了基本的了解。

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.