MOLECULAR GENETIC EPIDEMIOLOGY OF ENDOCARDIAL CUSHION DEFECTS

这项研究的中心目的是确定参与基因， AVCD和VSD的发病机制。 这将通过确定 候选基因中的多态性，并使用所述多态性进行遗传分析。 协会研究。 此外，候选基因内的多态性， 以及高度多态性的短串联重复序列多态性 （STRP），将用于全基因组连锁搜索中的基因， 多个受影响个体的大家庭。 协会或 连锁研究表明，参与一个特定的基因，一个搜索 基因突变将被执行。 此外，我们将确定 是否可能的候选染色体区域（染色体21q21.1-qter）是 参与非Downs AVCD，通过使用分子技术搜索 等位基因丢失、单亲二体和隐性易位。 我们建议研究与此相关的分子遗传变异性， 有内膜垫和室间隔发育的6组 受试者：1）患有房室管的唐氏综合征受试者 缺陷; 2）非Down受试者房室通道缺陷; 3）Down 无功能性心脏病的综合征患者; 4）正常人 没有心脏病或唐氏综合征; 5）唐氏综合征受试者， 膜周部室间隔缺损;和6）非Down受试者 膜周部室间隔缺损 考试将 在这些受试者的亲属中进行，以确定他们是否 有先天性心脏缺陷或任何其他先天性异常。 这 将通过获取家族谱系、病史和 检查一级亲属（如果阳性，则检查二级和三级亲属 利用超声心动图和心电图 技术.

The central purpose of this study is to identify genes involved in the pathogenesis of AVCDs and VSDs. This will be accomplished by identifying polymorphisms in candidate genes, and using the polymorphisms for genetic association studies. In addition, polymorphisms within candidate genes, as well as the highly polymorphic short tandem repeat polymorphisms (STRPs), will be used in a genome-wide linkage search for the gene in large families with multiple affected individuals. Should association or linkage studies suggest involvement of a specific gene, a search for mutations in the gene will be carried out. In addition, we will determine whether a likely candidate chromosomal region (chromosome 21q21.1-qter) is involved in non-Downs AVCD by using molecular techniques to search for allele loss, uniparental disomy, and cryptic translocations. We propose to investigate the molecular genetic variability associated with endocardial cushion and ventricular septal development in six groups of subjects: 1) Down syndrome subjects with atrioventricular canal defects; 2) non-Down subjects with atrioventricular canal defects; 3) Down syndrome subjects with no functional heart disease; 4) normal subjects with no heart disease or Down syndrome; 5) Down syndrome subjects with perimembranous interventricular septal defects; and 6) non-Down subjects with perimembranous interventricular septal defects. Examinations will be carried out in the relatives of these subjects to ascertain whether they have congenital heart defects or any other congenital anomalies. This will be accomplished by obtaining family pedigrees, medical histories, and examining 1st degree relatives (and, if positive, 2nd and 3rd degree relatives) utilizing echocardiographic and electrocardiographic techniques.