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
Pediatric Heart Center, Children's Hospital of Fudan University, Shanghai, China.
Shanghai Key Laboratory of Birth Defects, Shanghai, China.
Front Genet. 2025 May 8;16:1582718. doi: 10.3389/fgene.2025.1582718. eCollection 2025.
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.
先天性心脏病（CHD）常伴有左右侧缺陷（LD），形成一种严重且复杂的先天性异常形式。本研究旨在探索中国人群中CHD/LD的遗传病因。
我们在2008年1月至2019年8月期间招募了52个中国CHD家系三联体，每个家系包括一名CHD/LD先证者及其健康父母。对这些三联体的外周血样本进行全外显子组测序（WES）。通过WES结果的质量控制以及基于变异罕见性、有害性、遗传模式和基因功能的筛选方法，确定携带致病变异的候选基因。
共鉴定出两个候选基因以及46个携带功能丧失（LOF）变异的CHD相关基因。其中包括一个变异（在 中）、两个复合杂合变异（在 中）和一个X连锁隐性变异（在 中）。值得注意的是，与纤毛相关的基因变异频率最高。此外，26.1%（12/46）携带LOF变异的CHD相关基因与纤毛功能显著相关。
本研究在中国人群中鉴定出两个CHD/LD的新候选基因（ 和 ），其中纤毛基因在所有候选基因中出现频率最高。研究结果为中国人群中CHD/LD的遗传基础提供了关键见解，可能对遗传咨询和产前预防具有重要意义。
