- Congenital Heart Disease Center
Interdisciplinary Research Initiative
2/1/2007 - 1/31/2010
Michael Province, Patrick Y. Jay
Congenital heart disease is strongly influenced by genetic factors, and is the leading cause of infant deaths, yet there has been only limited progress in identifying particular genes that are responsible for only a small percentage of CHD cases. Parental consanguinity is a strong risk factor for CHD occurrence worldwide, but consanguineous pedigrees are uncommon in many parts of the world, including the United States, and so most family-based linkage studies to date have tested autosomal dominant hypotheses of CHD causation, with the interesting discovery that heterozygous mutations in cardiac transcription factors such as NKX2.5 and GATA4 can give rise to a wide variety of different cardiac phenotypes. However, recessive genes may also have great importance, but studies are limited by the lack of available consanguineous pedigrees. Such pedigrees are quite common in certain parts of the world, such as India. Building on connections from their former fellowship training programs at Yale University, a pediatric cardiologist (Dr. Sunita Maheshwari) and Clinical Geneticist Thomas Morgan, MD created an opportunity in Bangalore, India, to study recessive models of CHD. Linkage analysis of CHD probands born to consanguineous parents may lead to the discovery of novel genetic pathways to CHD in humans, which may then be further elucidated by the creation of animal models of CHD.