MOLECULAR GENETIC EPIDEMIOLOGY OF ENDOCARDIAL CUSHION DEFECTS

这项研究的中心目的是找出参与 室上性心动过速和室间隔缺损的发病机制。这将通过确定 候选基因的多态，并利用这些多态对遗传 协会研究。此外，候选基因的多态， 以及高度多态的短串联重复序列多态 (STRPs)，将用于对该基因的全基因组连锁搜索 有多个受影响个人的大家庭。是否应该联合或 连锁研究表明涉及特定的基因，搜索 基因的突变将被进行。此外，我们将确定 一个可能的候选染色体区域(染色体21q21.1-QTER)是否 利用分子生物学技术寻找非唐氏病相关的AVCD 等位基因丢失、单亲二体和隐蔽易位。 我们建议研究相关的分子遗传变异性。 心内膜垫与室间隔发育的关系 研究对象：1)伴有房室管的唐氏综合征患者 缺陷；2)非Down受试者合并房室管缺陷；3)Down 无功能性心脏病的综合征受试者；4)正常受试者 无心脏病或唐氏综合症；5)患有唐氏综合症的受试者 膜周型室间隔缺损；6)非Down受试者 伴有膜周室间隔缺陷症。考试将是 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畸形。这 将通过获取家族血统、病史和 检查一级亲属(如果是阳性，则检查二级和三级亲属 亲属)利用超声心动图和心电图仪 技巧。

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.