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.

OTOF基因突变是遗传性听力损失的常见原因，也是听神经病谱系障碍 (ANSD) 的主要原因。尽管据报道大多数OTOF突变患者具有稳定的、先天性或语前发作的重度至极重度听力损失，但部分患者表现出不典型的临床表型，而OTOF突变患者的基因型-表型相关性尚不完全清楚. 在这项研究中，我们旨在揭示OTOF相关听力损失患者的详细临床特征和基因型-表型相关性。我们数据库中被诊断为OTOF的 64 名患者可获得详细的临床信息- 相关的听力损失。如前所述，大多数患者（90.6%）表现出“典型”表型；语前和重度至重度听力损失。47 名患者（73.4%）接受了人工耳蜗植入手术并取得了成功；大约 85-90% 的患者在植入人工耳蜗后的听力水平为 20-39 分贝，听觉表现类别 (CAP) 等级为 6 级或更高。尽管截短突变和 p.Arg1939Gln 与严重表型明显相关，但几乎一半具有一种或多种非截短突变的患者表现出轻度至中度听力损失。值得注意的是，具有 p.His513Arg、p.Ile1573Thr 和 p.Glu1910Lys 的患者表现出“真正的”听神经病样临床特征。在这项研究中，我们阐明了基因型-表型相关性和人工耳蜗植入的疗效迄今为止研究的最大队列中与OTOF相关的听力损失患者。我们相信，本研究中发现的临床特征和基因型-表型相关性将支持对OTOF相关听力损失患者的术前咨询和适当干预。