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Targeted gene sequencing and hearing follow-up in 7501 newborns reveals an improved strategy for newborn hearing screening

European Journal of Human Genetics volume 33, pages 468–475 (2025)Cite this article

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Abstract

Hearing loss is a common congenital condition. Concurrent newborn hearing and limited genetic screening has been implemented in China for the last decade. However, the role of gene sequencing screening has not been evaluated. In this study, we enrolled 7501 newborns (52.7% male, 47.3% female) in our Newborn Screening with Targeted Sequencing (NESTS) program, and 90 common deafness genes were sequenced for them. Hearing status assessments were conducted via telephone from February 2021 to August 2022, for children aged 3 to 48 months. Of the universal newborn hearing screening, 126 (1.7%) newborns did not pass. Targeted sequencing identified 150 genetically positive newborns (2.0%), with 25 exhibiting dual-positive results in both screening. Following diagnostic audiometry revealed 18 hearing loss newborns and half of them had abnormal results in both screening. The positive predictive value for universal newborn hearing screening alone was merely 14.3% (18/126). However, when combined with targeted sequencing, this rate increased to 36.0% (9/25). Furthermore, limited genetic screening identified 316 carriers of hot-spot variants, but none exhibited biallelic variants. All 15 hot-spot carriers who failed physical screening demonstrated normal hearing during follow-up. In this cohort study of 7501 Newborns, Combining targeted sequencing with universal newborn hearing screening demonstrated technical feasibility and clinical utility of identifying individuals with hearing loss, especially when coupled with genetic counseling and closed-loop management. It is suggested to use this integrated method as an improved strategy instead of the current limited genetic screening program in some regions of China.

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Fig. 1: Enrollment and outcomes of newborns participating in this study.
Fig. 2: UNHS results of 7501 newborns and the comparison with TSNHS results and limited genetic screening.
Fig. 3: Comparison of hot-spot variants detection results between TSNHS and LGS.
Fig. 4: Mutation spectra of genetically positive cases.

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Data availability

There are restrictions to the availability of DNA sequencing data due to National regulations on the management of human genetic resources in China. Other de-identified enrolled patients’ data collected during the study will be made available on request.

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Acknowledgements

We thank all the participants who agreed to enroll in the study.

Funding

This work was supported by grants from the Beijing Municipal Science and Technology Commission Foundation (Z221100007422017), the National Natural Science Foundation of China (82000745), Funding for Birth Defects and Precision Medicine of Beijing Municipal Health Commission (2023 and 2024), and the Beijing Municipal Health Commission Foundation (2022-2-1142).

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Author notes

  1. These authors contributed equally: Chanjuan Hao, Xuyun Hu.

Authors and Affiliations

  1. Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

    Chanjuan Hao, Xuyun Hu, Ruolan Guo, Zhan Qi & Wei Li

  2. Henan Key Laboratory of Inherited Metabolic Diseases, Pediatric Research Institute of Zhengzhou Children’s Hospital, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, China

    Chanjuan Hao, Xuyun Hu, Ruolan Guo & Wei Li

  3. Shunyi Women and Children’s Healthcare Hospital of Beijing Children’s Hospital, Beijing, China

    Feng Jin, Xiaofen Zhang, Limin Xie & Yuanhu Liu

  4. Department of Otolaryngology Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

    Haihong Liu, Yuanhu Liu & Xin Ni

Authors
  1. Chanjuan Hao
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Contributions

Chanjuan Hao had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. CH, XN, and WL conceived and designed the study. XH, CH, RG, and WL contributed to panel design and gene curation. FJ, XZ, LX, and HL were involved in newborn recruitment and data collection. XH, CH, RG, and WL developed the in-house bioinformatics pipeline. FJ and XZ performed the clinical utility evaluation. XH prepared the manuscript. CH and WL revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Chanjuan Hao, Xin Ni or Wei Li.

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The authors declare no competing interests.

Ethical approval and consent to participate

This study received approval from the institutional review board of Beijing Children’s Hospital (2017-K-39). Written informed consents to participate were obtained from the parents of all newborns.

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Hao, C., Hu, X., Guo, R. et al. Targeted gene sequencing and hearing follow-up in 7501 newborns reveals an improved strategy for newborn hearing screening. Eur J Hum Genet 33, 468–475 (2025). https://doi.org/10.1038/s41431-024-01711-x

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