Mutational and phenotypic spectrum of OTOF-related auditory neuropathy in Koreans: eliciting reciprocal interaction between bench and clinics

• DOI: 10.1186/s12967-018-1708-z
• Publication Date: 2018-11-27T07:22:34Z
• Authors: Bong Jik Kim; Jeong Hun Jang; Jin Hee Han; Hye-Rim Park; Doo Yi Oh; Seungmin Lee; Min Young Kim; Ah Reum Kim; Chung Lee; Nayoung K. D. Kim; Woong-Yang Park; Yun-Hoon Choung; Byung Yoon Choi
• Keywords: Auditory neuropathy; Etiology

While auditory neuropathy spectrum disorder (ANSD) is a heterogeneous and its management quite varies depending upon the etiology, even including self-resolution, OTOF an important molecular etiology of prelingual ANSD has emerged as attractive target for implementation precision medicine in terms timing prognosis prediction rehabilitation. However, to date, literature lacking genotype–phenotype relationship this gene well efficient testing strategy clinic many populations make things more complicated Koreans, most prevalent variant p.Arg1939Gln among Korean children frequently evaded detection by next generation sequencing (NGS), resulting delayed genetic diagnosis late cochlear implantation (CI). The aims study are document mutational phenotypic OTOF-related (DFNB9) population, further establishing correlation proposing set commonly found variants be screened first. Genetic through NGS-based was made on patients with two tertiary hospitals. Genotype phenotypes eleven DFNB9 were reviewed. For data analysis, Mann–Whitney test Fisher's exact applied. This disclosed four Koreans: allele frequency 40.9%, p.Glu841Lys (13.6%), p.Leu1011Pro p.Arg1856Trp (9.1%). Three novel (c.4227 + 5G > C, p.Gly1845Glu, p.Pro1931Thr) identified. Interestingly, significant association worse ASSR thresholds observed despite consistently no ABR response. Ten 11 received CI rehabilitation, showing favorable outcomes rapid improvement early-CI group (age at ≤ 18 mo.) than late-CI group. included largest cohort date proposed frequent variants, allowing potential prioritization exons during Sanger sequencing. Further, homozygotes poor residual hearing observed. We may have suspect homozygosity cases putative negative solely NGS. Reciprocal feedback between bench clinics regarding would complement each other.