Abstract
Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype–phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype–phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a “typical” phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85–90% of the patients showed a hearing level of 20–39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed “true” auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype–phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype–phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.
Highlights
Hearing loss is one of the most common sensory disorders, with around 466 million people suffering from hearing loss (World Health Organization 2021)
We investigated the clinical data of the patients diagnosed with OTOF-related hearing loss registered in our database, and aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype–phenotype correlation in the patients with OTOF mutations
Detailed clinical information was available for 66 of 74 patients, and their clinical characteristics were analyzed retrospectively through the review of their medical records, and 2 of them were excluded because the clinical phenotype was completely incompatible with OTOF-related hearing loss: One of them had two mutations of uncertain significance and this case had late-onset ski-slope hearing loss, with the other having three mutations of uncertain significance and acute-onset unilateral mild hearing loss
Summary
Hearing loss is one of the most common sensory disorders, with around 466 million people suffering from hearing loss (World Health Organization 2021). OTOF is reported to be the causative gene of DFNB9 and one of the common causes. The prevalence of OTOF mutations has been reported to be 1.4–3.2% of non-syndromic hearing loss cases (Rodríguez-Ballesteros et al 2008; Choi et al 2009; Wang et al 2010a; Mahdieh et al 2012) and 1.72% in Japan (Iwasa et al 2019). More than 220 mutations in OTOF have been reported (Vona et al 2020). It is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, such as mild-to-moderate progressive cases (Chiu et al 2010). The genotype–phenotype correlation in the patients with OTOF mutations is, subsequently, not yet fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
