Deafness Gene Variations in a 1120 Nonsyndromic Hearing Loss Cohort: Molecular Epidemiology and Deafness Mutation Spectrum of Patients in Japan

Objectives: To elucidate the molecular epidemiology of hearing loss in a large number of Japanese patients analyzed using massively parallel DNA sequencing (MPS) of target genes. Methods: We performed MPS of target genes using the Ion PGM system with the Ion AmpliSeq and HiSeq 2000 systems using SureSelect in 1389 samples (1120 nonsyndronnic hearing loss cases and 269 normal hearing controls). We filtered the variants identified using allele frequencies in a large number of controls and 12 predication program scores. Results: We identified 8376 kinds of variants in the 1389 samples, and 409 835 total variants were detected. After filtering the variants, we selected 2631 kinds of candidate variants. The number of GJB2 mutations was exceptionally high among these variants, followed by those in CDH23, SLC26A4, MYO 15A, COL11A2, MYO7A, and OTOF. Conclusions: We performed a large number of MPS analyses and clarified the genetic background of Japanese patients with hearing loss. This data set will be a powerful tool to discover rare causative gene mutations in highly heterogeneous monogenic diseases and reveal the genetic epidemiology of deafness.