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.
Showing the most recent 10 out of 33 publications
