The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.
The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.
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DOI：
10.1161/circresaha.111.300297
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发表时间：
2013-02-15
影响因子：
20.1
通讯作者：
Rosenberg E
中科院分区：
文献类型：
--
作者：
Pediatric Cardiac Genomics Consortium;Gelb B;Brueckner M;Chung W;Goldmuntz E;Kaltman J;Kaski JP;Kim R;Kline J;Mercer-Rosa L;Porter G;Roberts A;Rosenberg E;Seiden H;Seidman C;Sleeper L;Tennstedt S;Kaltman J;Schramm C;Burns K;Pearson G;Rosenberg E
先天性心脏缺陷（CHD）是出生缺陷中婴儿死亡的主要原因，后期发病率和过早死亡率仍然是个问题。虽然遗传因素对冠心病的发生有重要作用，但大多数患者的具体遗传病变尚不清楚。美国国家心脏、肺和血液研究所资助的儿科心脏基因组学联盟建立了先天性心脏病遗传网络研究，以调查CHD中遗传因素、临床特征和结局之间的关系。儿科心脏基因组学联盟包括6个主要研究中心和4个卫星研究中心，在这些研究中心招募受试者，并收集医学数据和生物标本（血液、唾液、心血管组织）。核心基础设施包括一个行政/数据协调中心、生物库、数据中心和核心实验室（基因分型、全外显子组测序、候选基因评估和变异确认）。资格包括所有形式的CHD。对<1岁的先证者进行年度随访。家长们随时都可以报名。从2010年12月至2012年6月，共招募了3772名先证者。72%的先证者的父母一方或双方都参加了研究。先证者的中位年龄为5.5岁。每年联系三分之一的1岁以下儿童，了解后续情况。CHD的分布有利于更复杂的病变。大约11%的先证者有基因诊断。从97%和91%的血液和唾液样本中分别可以获得足够的DNA。先天性心脏病、房间隔缺损、圆锥动脉干和左心室流出道阻塞性病变的先证者的基因组分析正在进行中。欢迎科学界使用儿科心脏基因组学联盟的资源。
Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community’s use of Pediatric Cardiac Genomics Consortium resources is welcome.