Background: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects causing pulmonary hypertension, infective endocarditis, and even death. The important role of genetics in determining spontaneous ductal closure has been well-established. However, as many of the identified variants are rare, thorough identification of the associated genetic factors is necessary to further explore the genetic etiology of PDA. Methods: We performed whole-exome sequencing (WES) on 39 isolated nonsyndromic PDA patients and 100 healthy controls. Rare variants and novel genes were identified through bioinformatic filtering strategies. The expression patterns of candidate genes were explored in human embryo heart samples. Results: Eighteen rare damaging variants of six novel PDA-associated genes (SOX8, NES, CDH2, ANK3, EIF4G1, and HIPK1) were newly identified, which were highly expressed in human embryo hearts. Conclusions: WES is an efficient diagnostic tool for exploring the genetic pathogenesis of PDA. These findings contribute new insights into the molecular basis of PDA and may inform further studies on genetic risk factors for congenital heart defects.
Keywords: congenital heart defects; patent ductus arteriosus; rare variants; single-nucleotide polymorphism; whole-exome sequencing.
Copyright © 2022 Gao, Wu, Chen, Chen, Zhang and Zhao.