Targeted next generation sequencing reveals OTOF mutations in auditory neuropathy spectrum disorder

To study the genetic etiology of auditory neuropathy spectrum disorder (ANSD) in a Chinese family and perform a literature review of OTOF mutations and cochlear implantation (CI).

Sequential targeted next generation sequencing (NGS) and CI was performed for the proband. Further, 50 DNA samples from unrelated families with nonsyndromic deafness were examined for frequency determination. The impact of OTOF mutations on hearing recovery after CI was assessed through the literature survey.

In the proband, the targeted NGS panel revealed five suspected variants in four genes (OTOF, EYA4, PCDH15, and GIPC3), of which two mutations-c.5098G > C (p.Glu1700Gln) and c.1702C > T (p.Arg568Trp)-in the OTOF gene were found to be correlated with ANSD. The c.5098G > C allele was identified in only one child from the 50 unrelated participants. The proband's hearing and speech abilities were restored 2 years after the surgery. Most ANSD patients (90.9%; 30/33) with OTOF mutations have acceptable surgical outcomes, as indicated by existing reports.

Our results support the feasibility of CI for patients with ANSD and OTOF mutations, and this hypothesis was supported by the review of existing data. A larger number of cases studies is required to determine possible modifies on the prognosis of surgery.