AUTHOR=Gao Ying , Wu Dan , Chen Bo , Chen Yinghui , Zhang Qi , Zhao Pengjun 

TITLE=Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.921925

DOI=10.3389/fgene.2022.921925

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Eighteen rare damaging variants of six novel PDA-associated genes (<italic>SOX8</italic>, <italic>NES</italic>, <italic>CDH2</italic>, <italic>ANK3</italic>, <italic>EIF4G1</italic>, and <italic>HIPK1</italic>) were newly identified, which were highly expressed in human embryo hearts.</p><p><bold>Conclusions:</bold> 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.</p>