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Next-generation sequencing-based mutation analysis of genes associated with enlarged vestibular aqueduct in Chinese families

  • Otology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Objectives

The identification of gene mutations enables more appropriate genetic counseling and proper medical management for EVA patients. The purpose of this study was to validate the accuracy and sensitivity of our method for comprehensive mutation detection in EVA, and summarize these data to explore a more accurate and convenient genetic diagnosis method.

Methods

A multiplex PCR sequencing panel was designed to capture the exons of three known EVA-associated genes (SLC26A4, KCNJ10, and FOXI1), and NGS was conducted in 17 Chinese families with EVA.

Results

A total of 16 SLC26A4 variants were found in 21 probands with bilateral EVA, including three novel variants (c.416G>A, c.823G>A and c.1027G>C), which were not reported in the dbSNP, gnomAD database, and ClinVar databases. One patient carried a FOXI1 variant (heterozygous, c.214C>A) and one patient carried a KCNJ10 variant (heterozygous, c.1054C>A), both of which were novel variants. Biallelic potential pathogenic variants were detected in 21/21patient samples, leading to a purported diagnostic rate of 100%. All results were verified by Sanger sequencing.

Conclusion

This result supplemented the mutation spectrum of EVA, and supports that combined multiple PCR-targeted enrichment, and NGS is a valuable molecular diagnostic tool for EVA, and is suitable for clinical application.

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Funding

This study was funded by grants from the National Natural Science Foundation of China (Grant No. 81771023), the Postdoctoral Research Foundation of China (No. 2017M620359) and the Natural Science Foundation of Hunan Province (No. 2018JJ2634).

Author information

Authors and Affiliations

  1. Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China

    Yalan Liu, Jie Wen, Shushan Sang, Lingyun Mei, Chufeng He, Lu Jiang, Sida Huang & Yong Feng

  2. Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, 410008, Hunan, China

    Yalan Liu, Jie Wen, Shushan Sang, Lingyun Mei, Chufeng He, Lu Jiang, Sida Huang & Yong Feng

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  1. Yalan Liu
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Contributions

Conceptualization: YLL, YF; Methodology: YYL; Formal analysis and investigation: YYL, JW; Writing—original draft preparation: YYL; Pedigrees collection: SSS, LYM, CFH and LJ; Supervision: YF, LYM. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Yong Feng.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Medical Ethics Committee of Xiangya Hospital, Central South University (201403092) and is compliant with the Code of Ethics of the World Medical Association.

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Informed consent was obtained from all individual participants or their guardians included in the study.

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Liu, Y., Wen, J., Sang, S. et al. Next-generation sequencing-based mutation analysis of genes associated with enlarged vestibular aqueduct in Chinese families. Eur Arch Otorhinolaryngol 277, 3331–3339 (2020). https://doi.org/10.1007/s00405-020-06050-3

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