Genetic analysis of auditory neuropathy spectrum disorder in the Korean population

• Auditory neuropathy is caused by mutations in OTOF, DIAPH3, and PJVK genes.
• Gene screening of OTOF, DIAPH3, and PJVK genes were performed in 19 patients with AN.
• Two novel mutations in OTOF and DIAPH3 genes, were identified.
• The most common mutations of other populations were not detected in this study.
• There might be some novel ANSD-related genes specific to the Korean population.

Auditory neuropathy spectrum disorder (ANSD) is caused by dys-synchronous auditory neural response as a result of impairment of the functions of the auditory nerve or inner hair cells, or synapses between inner hair cells and the auditory nerve. To identify a causative gene causing ANSD in the Korean population, we conducted gene screening of the OTOF, DIAPH3, and PJVK genes in 19 unrelated Korean patients with ANSD. A novel nonsense mutation (p.Y1064X) and a known pathogenic mutation (p.R1939Q) of the OTOF gene were identified in a patient as compound heterozygote. Pedigree analysis for these mutations showed co-segregation of mutation genotype and the disease in the family, and it supported that the p.Y1064X might be a novel genetic cause of autosomal recessive ANSD. A novel missense variant p.K1017R (c.3050A>G) in the DIAPH3 gene was also identified in the heterozygous state. In contrast, no mutation was detected in the PJVK gene. These results indicate that no major causative gene has been reported to date in the Korean population and that pathogenic mutations in undiscovered candidate genes may have an effect on ANSD.