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Clinical application of whole exome sequencing (WES) in the genetic diagnosis of 768 Chinese patients with bilateral hearing loss

European Journal of Human Genetics (2025)Cite this article

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Abstract

Hearing loss is a prevalent sensory disability with strong genetic heterogeneity, affecting approximately 60% of patients due to genetic factors. To investigate the possible genetic causes of hearing loss in 768 unrelated Chinese patients and analyze the genetic diagnosis rates among patients with different clinical phenotypic characteristics, 768 patients were enrolled, and whole-exome sequencing (WES) was performed for genetic testing. Sanger sequencing, MLPA, or qPCR were used to verify the parental origin of identified variants. We identified possible genetic etiologies in 501 of the 768 patients (65.2%), including 456 with non-syndromic and 45 with syndromic hearing loss. A total of 214 variants from 30 genes were identified: 174 previously reported and 40 novel pathogenic/likely pathogenic variants, the 18 hotspot variants accounted for 71.9% of all identified variants. Notably, 15 patients carried de novo variants. The genetic diagnosis rate was significantly higher in patients with severe-profound hearing loss (95.8%, 474/495) compared to those with mild-moderate hearing loss (9.9%, 27/273), P < 0.001. Our findings expand the spectrum of genetic variants associated with hearing loss and demonstrate high genetic diagnosis rates in patients with severe-profound hearing loss and congenital onset. WES combined with parental origin verification is an effective and economical method for identifying the genetic etiology of hearing loss and can be considered a priority in clinical practice for guiding early intervention and preventing further hearing loss.

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Fig. 1: Different genetic diagnostic rates in patients with different clinical phenotypic characteristics.
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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

We thank the departmental staff for their assistance in the implementation of this work, and we are also very grateful to patients and their families included in the study for their support.

Funding

This work was supported by the National Key R&D Program of China (2018YFC1002206), Natural Science Foundation of Henan Province (232300420230, 242300420392) and Henan Provincial Key Scientific Research Project Plan of Higher Education Institution (25A310012).

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Authors and Affiliations

  1. Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Hongfei Kang, Huikun Duan, Lisha Su, Yanjie Xia, Zili Li & Xiangdong Kong

  2. Department of Education, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Jingjing Li

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  1. Hongfei Kang
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  2. Jingjing Li
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  7. Xiangdong Kong
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Contributions

X Kong and H Kang conceived and designed the project. H Kang and J Li summarized all the data. H Kang, H Duan, Y Xia, L Su and Z Li performed genetic testing. H Kang and X Kong recruited patients. H Kang and J Li wrote the manuscript with help from all authors.

Corresponding author

Correspondence to Xiangdong Kong.

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The authors declare no competing interests.

Ethical approval

This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Approval no.:KS-2018-KY-36).

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Kang, H., Li, J., Duan, H. et al. Clinical application of whole exome sequencing (WES) in the genetic diagnosis of 768 Chinese patients with bilateral hearing loss. Eur J Hum Genet (2025). https://doi.org/10.1038/s41431-025-01896-9

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