CARDIAC GENETICS REGISTRY FOR CONGENITAL CARDIOVASCULAR DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Current literature suggests that while etiologies remain complex, a number of congenital cardiac malformations can be linked to specific heritable factors. A broad multi-factorial model is gradually being replaced with disease specific models where independent genetic and/or teratogenic pathways may lead to a particular outcome. These genetic pathways include chromosome deletions, disruptions (translocations), duplications of particular genetic regions, point mutations involving single genes, or alterations in the ability for a gene to be transcribed into a functional protein. In recent years, researchers have identified associations between a number of cardiac syndromes and diagnostic molecular findings. Examples include identification of microdeletions of chromosome 7 (Williams syndrome) and chromosome 22 (Velo-cardio-facial syndrome) both of which clinically manifest cardiac and non-cardiac findings. Commercial cytogenetic probes have recently become available for these two genetic disorders, enabling standardized testing. Individuals with Williams syndrome have haploinsuffficiency for multiple genes. Additionally there are individuals and families with isolated vascular disease (supravalvar aortic stenosis) caused by mutations involving a single gene within the Williams syndrome region. Individuals with "Williams-like" vascular disease may pass on this condition as a dominant trait, although this condition is currently detectable only by using specific screening for elastin mutations. These individuals will show no abnormality using commercial cytogenetic testing for Williams syndrome, yet possess a significant risk of bearing offspring affected with vascular disease.