ABSTRACT
Congenital heart disease (CHD) is the most common congenital birth defect, manifesting as any structural cardiac abnormality. Heterotaxy (HTX) is a related class of birth defects characterized by misorientation of the organs along the left-right axis. The heart is particularly sensitive to disruption of proper organ situs because of its left-right asymmetry. While large-cohort sequencing studies have identified long lists of candidate CHD genes, their contribution to the disease mechanism must be studied. Such investigations can benefit from the wealth of developmental tools available to study Xenopus. Large brood sizes and easy manipulation of embryos provide statistical power crucial for a model of CHD and HTX. These diseases are rich with novel de novo mutations present in unique cases, with low allelic abundance and low rates of recurrence compared to other genetic diseases. Understanding plausible mechanisms of patient-derived CHD/HTX genes on cardiac structure is essential to improve diagnostics and therapeutics. These studies also provide developmental and cell biologists a stepping stone to discover surprising connections between embryological, signaling, and cell biology pathways.
