Understanding the Role of Ciliary Genes in Congenital Heart Disease Pathogenesis

摘要

Congenital heart disease (CHD) is the most common birth defect, affecting approximately 1% of infants born each year. While over 300 genes are already reported in its pathogenesis, the causes of most cases remain unknown and are likely due to undiscovered causal variants and interactions between genetic factors. Recently, our lab's forward genetic mouse mutagenesis screen identified 100 genes that cause CHD. These are enriched for function in cilia, which are important for cell signaling and left-right patterning of the body. We hypothesize that variants in cilia and cilia-transduced cell signaling genes, particularly in the sonic hedgehog pathway, disrupt heart development to cause CHD in humans. To test this hypothesis, we recruited a cohort of ~600 patients with CHD through the University of Pittsburgh Medical Center and performed whole exome sequencing.