Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population
ObjectiveCongenital 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.MethodsWe recruited 52 Chinese CHD family trios bet...
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Frontiers Media S.A.
2025-05-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1582718/full |
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| author | Jinxin Wang Jinxin Wang Weicheng Chen Weicheng Chen Xianghui Huang Xianghui Huang Xianghui Huang Han Gao Han Gao Zhiyu Feng Zhiyu Feng Chaozhong Tan Chaozhong Tan Quannan Zhuang Quannan Zhuang Yuan Gao Yuan Gao Shaojie Min Shaojie Min Yuquan Lu Yuquan Lu Feizhen Wu Maoxiang Qian Maoxiang Qian Weili Yan Weili Yan Weili Yan Wei Sheng Wei Sheng Wei Sheng Wei Sheng Guoying Huang Guoying Huang Guoying Huang Guoying Huang |
| author_facet | Jinxin Wang Jinxin Wang Weicheng Chen Weicheng Chen Xianghui Huang Xianghui Huang Xianghui Huang Han Gao Han Gao Zhiyu Feng Zhiyu Feng Chaozhong Tan Chaozhong Tan Quannan Zhuang Quannan Zhuang Yuan Gao Yuan Gao Shaojie Min Shaojie Min Yuquan Lu Yuquan Lu Feizhen Wu Maoxiang Qian Maoxiang Qian Weili Yan Weili Yan Weili Yan Wei Sheng Wei Sheng Wei Sheng Wei Sheng Guoying Huang Guoying Huang Guoying Huang Guoying Huang |
| author_sort | Jinxin Wang |
| collection | DOAJ |
| description | ObjectiveCongenital 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.MethodsWe 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.ResultsA total of two candidate genes and 46 CHD-related genes harboring LOF (loss-of-function) 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, cilia-related genes DNAH2 had the highest frequencies of variants. Additionally, 26.1% (12/46) of CHD-related genes harboring LOF variants were significantly linked to cilia function.ConclusionThis research identified two 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. |
| format | Article |
| id | doaj-art-6434556b5f094fc3a8c9bfe658bfc65d |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-6434556b5f094fc3a8c9bfe658bfc65d2025-08-20T02:16:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-05-011610.3389/fgene.2025.15827181582718Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese populationJinxin Wang0Jinxin Wang1Weicheng Chen2Weicheng Chen3Xianghui Huang4Xianghui Huang5Xianghui Huang6Han Gao7Han Gao8Zhiyu Feng9Zhiyu Feng10Chaozhong Tan11Chaozhong Tan12Quannan Zhuang13Quannan Zhuang14Yuan Gao15Yuan Gao16Shaojie Min17Shaojie Min18Yuquan Lu19Yuquan Lu20Feizhen Wu21Maoxiang Qian22Maoxiang Qian23Weili Yan24Weili Yan25Weili Yan26Wei Sheng27Wei Sheng28Wei Sheng29Wei Sheng30Guoying Huang31Guoying Huang32Guoying Huang33Guoying Huang34Pediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaFujian Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University at Xiamen (Xiamen Children’s Hospital), Fujian, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaResearch Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaResearch Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaFujian Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University at Xiamen (Xiamen Children’s Hospital), Fujian, ChinaResearch Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Shanghai, ChinaPediatric Heart Center, Children’s Hospital of Fudan University, Shanghai, ChinaShanghai Key Laboratory of Birth Defects, Shanghai, ChinaFujian Key Laboratory of Neonatal Diseases, Children’s Hospital of Fudan University at Xiamen (Xiamen Children’s Hospital), Fujian, ChinaResearch Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Shanghai, ChinaObjectiveCongenital 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.MethodsWe 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.ResultsA total of two candidate genes and 46 CHD-related genes harboring LOF (loss-of-function) 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, cilia-related genes DNAH2 had the highest frequencies of variants. Additionally, 26.1% (12/46) of CHD-related genes harboring LOF variants were significantly linked to cilia function.ConclusionThis research identified two 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.https://www.frontiersin.org/articles/10.3389/fgene.2025.1582718/fullcongenital heart diseaselaterality defectsChinese populationscandidate genespathogenic variants |
| spellingShingle | Jinxin Wang Jinxin Wang Weicheng Chen Weicheng Chen Xianghui Huang Xianghui Huang Xianghui Huang Han Gao Han Gao Zhiyu Feng Zhiyu Feng Chaozhong Tan Chaozhong Tan Quannan Zhuang Quannan Zhuang Yuan Gao Yuan Gao Shaojie Min Shaojie Min Yuquan Lu Yuquan Lu Feizhen Wu Maoxiang Qian Maoxiang Qian Weili Yan Weili Yan Weili Yan Wei Sheng Wei Sheng Wei Sheng Wei Sheng Guoying Huang Guoying Huang Guoying Huang Guoying Huang Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population Frontiers in Genetics congenital heart disease laterality defects Chinese populations candidate genes pathogenic variants |
| title | Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population |
| title_full | Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population |
| title_fullStr | Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population |
| title_full_unstemmed | Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population |
| title_short | Identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in Chinese population |
| title_sort | identification of candidate genes harboring pathogenic variants in congenital heart disease and laterality defects in chinese population |
| topic | congenital heart disease laterality defects Chinese populations candidate genes pathogenic variants |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1582718/full |
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