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. 2025 Jan 7;16(1):60.
doi: 10.3390/genes16010060.

Novel OTOG Variants and Clinical Features of Hearing Loss in a Large Japanese Cohort

Yasuhiro Arai  1 , Shin-Ya Nishio  2 , Shinichi Goto  3 , Yumiko Kobayashi  4 , Yohei Honkura  5 , Akira Ganaha  6 , Kotaro Ishikawa  7 , Shin-Ichiro Oka  8 , Hiroshi Futagawa  9 , Mayuri Okami  10 , Fumio Takada  11 , Kyoko Nagai  12 , Tomoko Esaki  13 , Takayuki Okano  14 , Yumi Ohta  15 , Shin Masuda  16 , Kentaro Egusa  17 , Masato Teraoka  18 , Kazuma Sugahara  19 , Shin-Ichi Usami  2
Affiliations

Novel OTOG Variants and Clinical Features of Hearing Loss in a Large Japanese Cohort

Yasuhiro Arai et al. Genes (Basel). .

Abstract

Background/objectives: The OTOG gene is responsible for autosomal recessive non-syndromic sensorineural hearing loss and is assigned as DFNB18B. To date, 44 causative OTOG variants have been reported to cause non-syndromic hearing loss. However, the detailed clinical features for OTOG-associated hearing loss remain unclear.

Methods: In this study, we analyzed 7065 patients with non-syndromic hearing loss (mean age 26.4 ± 22.9 years, 2988 male, 3855 female, and 222 without gender information) using massively parallel DNA sequencing for 158 target deafness genes. We identified the patients with biallelic OTOG variants and summarized the clinical characteristics.

Results: Among the 7065 patients, we identified 14 possibly disease-causing OTOG variants in 26 probands, with 13 of the 14 variants regarded as novel. Patients with OTOG-associated hearing loss mostly showed congenital or childhood-onset hearing loss. They were considered to show non-progressive, mild-to-moderate hearing loss. There were no symptoms that accompanied the hearing loss in OTOG-associated hearing loss patients.

Conclusions: We confirmed non-progressive, mild-to-moderate hearing loss as the clinical characteristics of OTOG-associated hearing loss. These findings will contribute to a better understanding of the clinical features of OTOG-associated HL and will be useful in clinical practice.

Keywords: DFNB18B; OTOG; congenital hearing loss; mild-to moderate hearing loss; non-progressive hearing loss; non-syndromic hearing loss; otogelin.

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Conflict of interest statement

All authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Pedigrees and hearing thresholds for the OTOG-associated HL patients identified in this study. Solid line: hearing threshold in the right ear; Dashed line: hearing threshold in the left ear.
Figure 1
Figure 1
Pedigrees and hearing thresholds for the OTOG-associated HL patients identified in this study. Solid line: hearing threshold in the right ear; Dashed line: hearing threshold in the left ear.
Figure 2
Figure 2
Detailed progression analysis of HL deterioration for patients with OTOG-associated HL. The dotted line indicates the linear regression. Each dot indicates the pure-tone average (PTA) and age of each patient. COR data were used instead of pure-tone audiometry in cases under the age of 5 y.o.
See this image and copyright information in PMC

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