Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease

Liu,Xiao; Zhou,Jing‑Lin; Yang,Cheng-Ying; Zhou,Hai-Yan; He,Wen-Bin; Yang,Jing

doi:10.3892/mmr.2025.13563

Novel compound heterozygous mutation in DNAH9 causes complex congenital heart disease

Authors:
- Xiao Liu
- Jing‑Lin Zhou
- Cheng-Ying Yang
- Hai-Yan Zhou
- Wen-Bin He
- Jing Yang
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Affiliations: Department of Maternity, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China, Department of Genetics, Hunan Guangxiu Hospital Affiliated with Hunan Normal University, Hunan Normal University Health Science Centre, Changsha, Hunan 410017, P.R. China
Published online on: May 12, 2025 https://doi.org/10.3892/mmr.2025.13563
Article Number: 198
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Congenital heart disease (CHD) is the most common birth defect, affecting 2‑8% of newborns, with a marked impact on neonatal health. In the present study, the parents of a fetus diagnosed with CHD were recruited to investigate the genetic causes of this condition. Whole exome sequencing was conducted on tissue obtained from the fetus. A compound heterozygous mutation in the dynein axonemal heavy chain 9 (DNAH9) gene, comprising c.11176C>T (p.Arg3726Trp) and c.3743+1G>T, was identified. The c.11176C>T mutation has been previously reported as likely pathogenic, and c.3743+1G>T is a novel mutation. Sanger sequencing was employed for pedigree analysis. In addition, bioinformatics analyses were performed to predict the pathogenicity of the identified mutations, while in silico and minigene analyses were conducted to examine the splicing patterns associated with the splicing mutation. Software predictions and minigene analysis revealed that the c.3743+1G>T mutation leads to abnormal splicing. According to the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, the two identified DNAH9 mutations were classified as likely pathogenic. The present study identified the pathogenic variants in the affected family and expanded the mutation spectrum of the DNAH9 gene. It also provided a foundation for genetic counseling and reproductive intervention.

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