Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population

• Published in: Frontiers in genetics Vol. 16; p. 1582718
• Main Authors: Wang, Jinxin, Chen, Weicheng, Huang, Xianghui, Gao, Han, Feng, Zhiyu, Tan, Chaozhong, Zhuang, Quannan, Gao, Yuan, Min, Shaojie, Lu, Yuquan, Wu, Feizhen, Qian, Maoxiang, Yan, Weili, Sheng, Wei, Huang, Guoying
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.05.2025
• Subjects: candidate genes; Chinese populations; congenital heart disease; Genetics; laterality defects; pathogenic variants; congenital heart disease; Chinese populations; laterality defects; candidate genes; pathogenic variants
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2025.1582718

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. 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. A total of two candidate genes and 46 CHD-related genes harboring LOF (loss-of-function) variants were identified. These included one variants (in ), two compound heterozygous variants (in ), and one X-linked recessive variants (in ). Significantly, cilia-related genes had the highest frequencies of variants. Additionally, 26.1% (12/46) of CHD-related genes harboring LOF variants were significantly linked to cilia function. This research identified two novel candidate genes ( , and ) for CHD/LD in the Chinese population, with 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.