The Research Institute at Nationwide Children's Hospital Genetics of Congenital Heart Disease (CHD)

Congenital heart disease (CHD) is the most common type of birth defect, but the cause for the majority of cardiac birth defects remains unknown. Numerous epidemiologic studies have demonstrated evidence that genetic factors likely play a contributory, if not causative, role in CHD. A few genes have been identified by us and other investigators using traditional genetic approaches, but these genes only account for a small portion of the non-syndromic CHDs. Therefore, we are now utilizing whole exome sequencing (WES) and whole genome sequencing (WGS), with the addition of more traditional genetic techniques such as chromosomal microarray or traditional linkage analysis, to identify genetic causes of familial and isolated CHD. With WES/WGS, we are able to sequence all of the genes of an individual and apply different data analysis techniques based on whether we are analyzing a multiplex family or a cohort of trios (mother, father and child with CHD) with a specific isolated CHD. Therefore, WES/WGS is a robust method for identification of novel genetic causes of CHD, which will have important diagnostic and therapeutic consequences for these children. Subjects provided blood samples, skin biopsy, or saliva samples for DNA extraction and creation of cell lines. Tissue remaining after surgical procedures was also collected. Medical records were searched for detailed phenotype data and subjects were followed longitudinally for outcome.]]>
This study contains multiplex families, trios, duos and singletons from Nationwide Children's Hospital's cohort of CHD subjects. Individuals were recruited if they had congenital heart disease confirmed by echocardiography, cardiac catheterization, or direct surgical observation. Additional family members were also recruited, including both parents, and for multiplex families, both other affected and unaffected individuals. Inclusion criteria were any CHD that required intervention. Exclusion criteria were a known syndromic diagnosis, or presence of multiple extra-cardiac birth defects. ]]>
This study has been supported by the National Institutes of Health (NIH) / National Heart, Lung, and Blood Institute (NHLBI) via three awards: R01HL109758 (9/24/2012 - 7/31/2017) "Exome Sequencing and Functional Studies in Familial CHD" R21HL106549 (12/1/2010 - 11/30/2012) "Exome Sequencing in Familial Cardiovascular Malformations" R01HL090506 (05/15/2008 - 05/15/2012) "Genome-wide association study of HLHS and related disorders" ]]>