Screening mutations of OTOF gene in Chinese patients with auditory neuropathy, including a familial case of temperature-sensitive auditory neuropathy.

Background: Mutations in OTOF gene, encoding otoferlin, cause DFNB9 deafness and non-syndromic auditory neuropathy (AN). The aim of this study is to identify OTOF mutations in Chinese patients with non-syndromic auditory neuropathy.

Methods: 73 unrelated Chinese Han patients with AN, including one case of temperature sensitive non-syndromic auditory neuropathy (TS-NSRAN) and 92 ethnicity-matched controls with normal hearing were screened. Forty-five pairs of PCR primers were designed to amplify all of the exons and their flanking regions of the OTOF gene. The PCR products were sequenced and analyzed for mutation identification.

Results: Five novel possibly pathogenic variants (c.1740delC, c.2975_2978delAG, c.1194T>A, c.1780G>A, c.4819C > T) were identified in the group of 73 AN patients, in which two novel mutant alleles (c.2975_2978delAG + c.4819C > T) were identified in one Chinese TS-NSRAN case. Besides, 10 non-pathogenic variants of the OTOF gene were found in AN patients and controls.

Conclusions: Screening revealed that mutations in the OTOF gene account for AN in 4 of 73(5.5%) sporadic AN patients, which shows a lower genetic load of that gene in contrast to the previous studies based on other populations. Notably, we found two novel mutant alleles related to temperature sensitive non-syndromic auditory neuropathy. This mutation screening study further confirms that the OTOF gene contributes to ANs and to TS-NSRAN.