Audiological Phenotype, Natural History, and Intervention in Chinese Patients With Auditory Neuropathy Caused by OTOF Variants

Hongyang Wang; Kaili Wu; Jin Li; Mengqian Zhang; Xin Gao; Jing Guan; Lan Lan; Linyi Xie; Fen Xiong; Qiujing Zhang; Xiaochuan Xu; Danyang Li; Dayong Wang; Qiuju Wang

doi:10.1097/AUD.0000000000001801

Audiological Phenotype, Natural History, and Intervention in Chinese Patients With Auditory Neuropathy Caused by OTOF Variants

Ear Hear. 2026 May 18;47(4):1067-1079. doi: 10.1097/AUD.0000000000001801. Online ahead of print.

Authors

Hongyang Wang^{1

2

3

4

5}, Kaili Wu^{6

5}, Jin Li^{1

2

3

4

5}, Mengqian Zhang¹, Xin Gao¹, Jing Guan^{1

2

3

4}, Lan Lan^{1

2

3

4}, Linyi Xie^{1

2

3

4}, Fen Xiong^{1

2

3

4}, Qiujing Zhang^{1

2

3

4}, Xiaochuan Xu^{1

2

3

4}, Danyang Li^{1

2

3

4}, Dayong Wang^{1

2

3

4}, Qiuju Wang^{1

2

3

4}

Affiliations

¹ Department of Audiovestibular Medicine, Senior Department of Otolaryngology, Head and Neck Surgery, the Sixth Medical Center of Chinese People's Liberation Army General Hospital, Medical School of Chinese PLA, Beijing, China.
² Senior Department of Otolaryngology Head and Neck Surgery, the 6th Medical Center of Chinese PLA General Hospital, State Key Laboratory of Hearing and Balance Science, Beijing, China.
³ National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital, Beijing, China.
⁴ Key Laboratory of Hearing Science, Ministry of Education, Beijing, China.
⁵ These authors contributed equally to this work.
⁶ Department of Otorhinolaryngology-Head and Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.

Abstract

Objectives: To explore the correlations between genotype and phenotype, disease progression, and outcomes of interventions in patients with auditory neuropathy (AN) caused by OTOF gene variants.

Design: Patients with AN associated with OTOF variants were identified using whole-exome or panel sequencing. Variants were interpreted according to the American College of Medical Genetics and Genomics guidelines. Audiometric tests were conducted, including auditory brainstem response, distortion product otoacoustic emission (DPOAE), behavioral audiometry/pure-tone audiometry, etc. The genetic and audiological characteristics of the patients were analyzed. The disease progression and intervention of the patients were followed up, and phenotype differences were analyzed in combination with genotype.

Results: A total of 43 AN patients were identified with OTOF gene variants, including seven novel variants. The pure-tone average was 89.20 ± 17.81 dB HL, with 91.11% having severe hearing loss or greater. The auditory steady-state response and DPOAE results deteriorated with increasing disease duration. Twenty-five patients underwent cochlear implantation, with the Category of Auditory Performance score of 7.00 (5.00, 7.50). Patients with biallelic loss-of-function variants showed a trend toward worse hearing but a higher DPOAE response rate. Similarly, patients with a single allele variant causing protein truncation also had a higher DPOAE extraction rate.

Conclusions: Seven novel mutations of the OTOF gene were identified, which enriched the spectrum of OTOF gene variants. Most of the AN patients with OTOF variants showed severe to profound hearing loss, with the progression of the disease course. The cochlear implantation effects were good, which were related to the intervention age and duration. There is a correlation trend between OTOF variants' genotype and phenotype.

Keywords: Auditory neuropathy; Cochlear implantation; Genotype; Phenotype.

Abstract

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