ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1582718
This article is part of the Research TopicAdvancements in Congenital Heart Disease: Diagnosis and Management InnovationsView all articles
Identification of Candidate Genes Harboring Pathogenic Variants in Congenital Heart Disease and Laterality Defects in Chinese population
Provisionally accepted
Jinxin Wang1
Weicheng Chen1
Xianghui Huang2Han Gao1Zhiyu Feng1Chaozhong Tan1Quannan Zhuang1
YUAN GAO1Shaojie Min1Yuquan Lu1
Feizhen Wu1
Maoxiang Qian1
Weili Yan1
Wei Sheng1*
Guoying Huang1- 1Children's Hospital, Fudan University, Shanghai, China
- 2Fujian Key Laboratory of Neonatal Diseases, Xiamen Children’s Hospital, Xiamen, Fujian Province, China
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Objective Congenital heart disease (CHD) is often accompanied by laterality defects (LD), giving rise to a severe and intricate form of congenital anomaly. The aim of this study was to explore the genetic etiology of CHD/LD in the Chinese population. Methods We recruited 52 Chinese CHD family trios between January 2008 and August 2019, each comprising a CHD/LD proband and their healthy parents. Whole exome sequencing (WES) was carried out on peripheral blood samples from these trios. Candidate genes harboring pathogenic variants were determined through quality control of WES results and a screening approach based on variant rarity, deleteriousness, inheritance patterns, and gene function. Results A total of 2 candidate genes and 46 CHD-related genes harboring LOF (loss-offunction) variants were identified. These included one de novo variants (in DNAH2), two compound heterozygous variants (in DNAH2), and one X-linked recessive variants (in FLNA). Significantly, ciliarelated genes DNAH2 had the highest frequencies of variants. Additionally, 26.1% (12/46) of CHDrelated genes harboring LOF variants were significantly linked to cilia function. Conclusions This research identified 2 novel candidate genes ( DNAH2, and FLNA) for CHD/LD in the Chinese population, with DNAH2 ciliary genes being the most frequently occurring among all candidate genes. The results offer critical insights into the genetic basis of CHD/LD in the Chinese population, which may have implications for genetic counseling and prenatal prevention.
Keywords: congenital heart disease, laterality defects, Chinese populations, candidate genes, Pathogenic variants
Received: 24 Feb 2025; Accepted: 22 Apr 2025.
Copyright: © 2025 Wang, Chen, Huang, Gao, Feng, Tan, Zhuang, GAO, Min, Lu, Wu, Qian, Yan, Sheng and Huang. 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) or licensor 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.
* Correspondence: Wei Sheng, Children's Hospital, Fudan University, Shanghai, China
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