To identify novel genes for congenital heart defects using modern genomics
Lacking the full spectrum of their genetic architecture and the inability to study beating human cardiac cells in vitro has thwarted advances in the understanding and treatment of cardiac disorders Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for significant morbidity and mortality Congenital heart defects (CHDs) are structural abnormalities of the heart and great vessels that are present from birth Both genetic and non-genetic factors have been linked to cardiomyopathies and CHD pathogenesis Indeed, more than 100 genes have been identified in cardiomyopathies and CHDs, including troponins (cardiac troponin T type-2 (TNNT2), myosin binding protein C (MYBPC3) and Myosin Heavy Chain (MYH7) and transcriptions factors (ZIC3) I am interested in investigating the cardiomyopathy and CHD families with autosomal recessive inheritance as well as singlet/sporadic cardiomyopathy and CHD cases Sanger sequencing (gene level) and allele-specific PCR (pathogenic variants) of the important cardiomyopathy genes (eg MYH7, and MYBPC3) and CHD genes (ZIC3, NODAL and CFC1) will be performed on the probands of the families and will be followed by exome sequencing Results will be interesting and unique with understanding that detailed genetic architecture has not been investigated in this population The study will be helpful for genetic counseling and follow up disease management