FAMILY STUDY OF CONGENITAL CARDIOVASCULAR MALFORMATIONS

先天性心血管畸形（CCVM）的家族聚集性， 已经很好地建立了，但潜在的病因机制还没有 明白 我们在一个合作项目中的初步研究 巴尔的摩-华盛顿地区CCVM的基于人群的调查 表明有家族聚集性，可能是单基因的 遗传性左流出道缺损;我们的额外临床 研究已经确定了可能的形式fruste心脏表现， 一些家庭。 在拟定的项目中，综合临床评价 正式的遗传分析将确定可能的来源， 可变心脏表型的家族聚集。 分析将 对核心家族成员的表型数据进行了分析， 临床评估和二维和多普勒超声心动图， 包括M模式测量。 调查与之相关的风险 左流出道缺损、左发育不良患儿家属 将研究心脏综合征或主动脉缩窄。 为了比较 缺陷发生的家庭风险和类型，儿童的亲属 将对大动脉D型转位患者进行评估。 临床 评估对照家庭获得额外的家庭亲属 有记录的心脏缺陷成员。 该协议将最大限度地 使用逻辑回归的正式遗传分析的效率 方法. 这项研究将提供：（a）更好地了解病因 异常心脏表型之间的关系;（B）关于 在具有特定类型的先证者亲属中发生CCVM的风险 心脏畸形;（c）阐明风险因素或协变量 与这些畸形相关;（d）遗传模型拟合，以确定 这些缺陷的最吝啬的遗传模式;（e） 通过人类分子研究产生待检验的假设 和/或动物模型的开发;和（f）鉴定 为将来的遗传学研究提供信息。

Familial aggregation of congenital cardiovascular malformations (CCVM) has been well established, but the underlying etiologic mechanisms are not understood. Preliminary studies from our collaborative efforts in a population-based investigation of CCVM in the Baltimore-Washington area suggest a concentration of familial aggregation and possibly monogenic inheritance of some left outflow tract defects; our additional clinical studies have identified possible forme fruste cardiac manifestations in some families. In the proposed project, comprehensive clinical evaluation of pedigrees and formal genetic analyses will identify possible sources of familial aggregation of variable cardiac phenotypes. Analyses will be performed on phenotypic data from nuclear family members obtained during clinical assessments and 2 dimensional and Doppler echocardiography, including M-mode measurements. To investigate the risks associated with left outflow tract defects, the families of children with hypoplastic left heart syndrome or coarctation of the aorta will be studied. For comparison of familial risk for occurrence and types of defects, relatives of children with d-transposition of the great arteries will be evaluated. Clinical assessment of control families obtain additional relatives of family members with documented heart defects. This protocol will maximize the efficiency of the formal genetic analysis using logistic regressive methods. This study will provide: (a) better understanding of etiologic relationships among abnormal cardiac phenotypes; (b) information concerning risk of occurrence of CCVM in relatives of probands with specific types of cardiac malformations; (c) elucidation of risk factors or covariates associated with these malformations; (d) genetic model fitting to determine the most parsimonious patterns of inheritance for these defects; (e) generation of hypotheses to be tested through molecular studies in humans and/or the development of animal models; and (f) identification of informative pedigrees for future genetic studies.