Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Zhuo Meng¹  Qingjie Wang¹  Kai Bai¹  Shuang Zhou¹  Shiwei Jiang¹  Jian Wang¹  Kun Sun¹  Yue Zhou¹  Mei Yang¹  Hualin Wang¹  Sun Chen¹  Yu Wang² 

[1] Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Department of Pediatric Cardiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China;

关键词: whole-exome sequencing;    congenital heart disease;    right ventricular outflow tract obstruction;    pulmonary valvular stenosis;    pulmonary atresia with intact ventricular septum;    single nucleotide polymorphism;   

DOI  :  10.3389/fcvm.2021.811156

 received in 2021-11-08, accepted in 2021-12-30,  发布年份 2022

来源: Frontiers

【 摘 要 】

BackgroundPulmonary atresia (PA) is a kind of congenital heart disease characterized by right ventricular outflow tract obstruction. It is divided into PA with intact ventricular septum (PA/IVS) whose favorable form is pulmonary valvular stenosis (PS), and PA with ventricular septal defect (PA/VSD) whose favorable form is tetralogy of Fallot (TOF). Due to limitations in genetics etiology, whole-exome sequencing (WES) was utilized to identify new variants associated with the diseases.MethodsThe data from PS-PA/IVS (n = 74), TOF-PA/VSD (n = 100), and 100 controls were obtained. The common sites between PS and PA/IVS, PA/VSD and TOF, were compared. The novel rare damage variants, and candidate genes were identified by gene-based burden analysis. Finally, the enrichment analysis of differential genes was conducted between case and control groups.ResultsSeventeen rare damage variants located in seven genes were predicted to be associated with the PS through burden analysis. Enrichment analysis identified that the Wnt and cadherin signaling pathways were relevant to PS-PA/IVS.ConclusionThis study put forth seven candidate genes (APC, PPP1R12A, PCK2, SOS2, TNR, MED13, and TIAM1), resulting in PS-PA/IVS. The Wnt and cadherin signaling pathways were identified to be related to PS-PA/IVS by enrichment analysis. This study provides new evidence for exploring the genetic mechanism of PS-PA/IVS.

【 授权许可】

Unknown   
Copyright © 2022 Zhou, Bai, Wang, Meng, Zhou, Jiang, Wang, Wang, Yang, Wang, Sun and Chen.