Background Patent Ductus Arteriosus (PDA) is one of the most common congenital heart defects that can cause pulmonary hypertension, heart failure, and even death. Prior studies have suggested a role for genetics in determining spontaneous ductal closure, however the clinical characteristics and genetic cause underlying PDA remain unclear.
Results Therefore, to further explore genetic etiology of PDA, we applied Whole-exome Sequencing (WES) in 39unrelated isolated, non-syndromic PDApatientsand 100 healthy controls. Through a series of bio-information filtering strategies, the candidate genes are prioritized by comprehensively considering factors such as genefunctional enrichment, expression pattern and mutation burden during heart development. 18 rare damage variants of 6 total novel genes (SOX8, NES, CDH2, ANK3, EIF4G1, HIPK1)were identified for the first time and these pathogenic candidates are also highly expressed in the heart of human embryos.
Conclusions WES is an efficient diagnostic tool for identifying PDA related genes. The finding of our study contributes new insights into the molecular basis of PDA and may inform further studies on genetic risk factors for this congenital birth defect.