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Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing
BACKGROUND: Pulmonary 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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818757/ https://www.ncbi.nlm.nih.gov/pubmed/35141295 http://dx.doi.org/10.3389/fcvm.2021.811156 |
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author | Zhou, Yue Bai, Kai Wang, Yu Meng, Zhuo Zhou, Shuang Jiang, Shiwei Wang, Hualin Wang, Jian Yang, Mei Wang, Qingjie Sun, Kun Chen, Sun |
author_facet | Zhou, Yue Bai, Kai Wang, Yu Meng, Zhuo Zhou, Shuang Jiang, Shiwei Wang, Hualin Wang, Jian Yang, Mei Wang, Qingjie Sun, Kun Chen, Sun |
author_sort | Zhou, Yue |
collection | PubMed |
description | BACKGROUND: Pulmonary 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. METHODS: The 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. RESULTS: Seventeen 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. CONCLUSION: This 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. |
format | Online Article Text |
id | pubmed-8818757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88187572022-02-08 Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing Zhou, Yue Bai, Kai Wang, Yu Meng, Zhuo Zhou, Shuang Jiang, Shiwei Wang, Hualin Wang, Jian Yang, Mei Wang, Qingjie Sun, Kun Chen, Sun Front Cardiovasc Med Cardiovascular Medicine BACKGROUND: Pulmonary 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. METHODS: The 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. RESULTS: Seventeen 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. CONCLUSION: This 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. Frontiers Media S.A. 2022-01-24 /pmc/articles/PMC8818757/ /pubmed/35141295 http://dx.doi.org/10.3389/fcvm.2021.811156 Text en Copyright © 2022 Zhou, Bai, Wang, Meng, Zhou, Jiang, Wang, Wang, Yang, Wang, Sun and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Zhou, Yue Bai, Kai Wang, Yu Meng, Zhuo Zhou, Shuang Jiang, Shiwei Wang, Hualin Wang, Jian Yang, Mei Wang, Qingjie Sun, Kun Chen, Sun Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing |
title | Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing |
title_full | Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing |
title_fullStr | Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing |
title_full_unstemmed | Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing |
title_short | Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing |
title_sort | identification of rare variants in right ventricular outflow tract obstruction congenital heart disease by whole-exome sequencing |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818757/ https://www.ncbi.nlm.nih.gov/pubmed/35141295 http://dx.doi.org/10.3389/fcvm.2021.811156 |
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