Cardiovascular Diseases Clinical Trial
To identify genes involved in the pathogenesis of three types of congenital heart disease, atrial septal defects, paramembranous ventricular septal defects, and atrioventricular canal defects.
BACKGROUND:
Congenital heart defects (CHDs) are thought to result from genetic and environmental factors
that disturb cardiac embryogenesis. Because families with multiple members affected with
atrial septal defects (ASDs) and atrioventricular canal defects (AVCDs) have been described
in previous studies, and the paramembranous ventricular septum is in part completed by the
formation of the atrioventricular cushions, this project describes a genetic-epidemiologic
study of ASDs, paramembranous ventricular septal defects (VSDs), and AVCDs
DESIGN NARRATIVE:
The study is one of several subprojects within a Specialized Center of Research (SCOR) in
Pediatric Cardiovascular Disease. Three groups of subjects, each with surgically- or
echocardiographically-confirmed diagnoses of ASDs, VSDs or AVCDs have been identified for
study at the University of Iowa Hospitals and Clinics, and at Wolfson Children's Hospital in
Jacksonville, Florida. A fourth group of older subjects with ASDs and their progeny will be
studied at Iowa because of the reported high recurrence of heart disease in the offspring of
subjects with ASDs. The strategy calls upon the molecular genetic capacities available at
the University of Iowa to carry out genome-wide searches for genetic loci involved in these
defects. Several candidate regions have been identified for ASDs, VSDs and AVCDs. In
addition, three well-recognized syndromes provide additional candidate regions - Down
syndrome, Holt-Oram syndrome and 8p-syndrome. Parent-affected child trios will be genotyped
for closely-spaced markers within these regions and linkage disequilibrium analysis will be
used to narrow or exclude these candidate intervals. A genome-wide association study of the
trios will employ a parsimonious technique in which DNA from cases with the same CHD
phenotype will be pooled, and compared to the pooled DNA from their parents. Loci will be
identified where the allele frequency distributions in the affected children and their
parents are significantly different. When such loci are identified, a finer localization of
the chromosomal area will be undertaken using a high-density set of short tandem repeat
polymorphic markers that spans each of the candidate intervals.
The study completion date listed in this record was obtained from the "End Date" entered in
the Protocol Registration and Results System (PRS) record.
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