The familial clustering of congenital heart disease (CHD) has long suggested a role for genetic mutations, but the extent to which mutations contribute is poorly defined. In a few cases disease genes have been identified by linkage analysis in extended pedigrees, but the rarity of large, affected families limits the pace of discovery. In contrast, significant progress has been made in transgenic and knockout mouse models of cardiac development, suggesting new candidate genes for human CHD.

Overview of Project 4

Our goal is to identify genes that are important in the pathogenesis of CHD using a candidate gene approach. We are currently investigating the role that selected candidate genes play in the development of two forms of human CHD that are among the most common in children, and which cause significant morbidity in adults. The proposal takes advantage of the clinical resources at Children's Hospital-Boston, a major pediatric cardiology referral center.

As molecular mechanisms underlying cardiovascular development become elucidated, they are likely to have both medical and reproductive implications. With improved surgical palliation of congenital heart disease, caregivers are faced with new challenges associated with childbearing, not the least of which includes recurrence risk. Research performed in this component of the PGA may help provide individual families with recurrence risks based on genetic rather than empiric data, and may elucidate additional non-cardiac roles for the candidate genes analyzed.

Pediatric Cardiovascular Registry

This PGA utilizes a DNA registry focused on individuals and families with congenital cardiovascular disease. The registry provides the groundwork for multiple ongoing resident and collaborative investigations.

The registry is responsible for coordinating clinical care/research efforts in genetic cardiology (identifying collaborators in cardiology, genetics, and genetic research within Children’s Hospital / Enders Research community, identifying potential joint projects), preparing educational materials, developing resources for physician education, and creating patient/donor information pamphlet or newsletters as appropriate.

Congenital Cardiovascular Genetics

Children’s Hospital Boston has developed within its Cardiology Department a Congenital Cardiovascular Genetics Program. The program’s goal is to provide care, services and access to research for families with congenital cardiovascular disease whose etiology is likely genetic.

One mechanism identified to improve this standard of care has been the creation of a website describing congenital cardiovascular genetic clinical care and research available through the Children’s Hospital program as well as resources identified in the larger national and international community. For more information, visit our Congenital Cardiovascular Genetics Program website.

For questions or feedback, please e-mail us: Cardiovasculargenetics@cardio.chboston.org