Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients

Kentaro Mori; Hideaki Moteki; Maiko Miyagawa; Shin-Ya Nishio; Shin-Ichi Usami

doi:10.1371/journal.pone.0162230

Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients

PLoS One. 2016 Sep 14;11(9):e0162230. doi: 10.1371/journal.pone.0162230. eCollection 2016.

Authors

Kentaro Mori¹, Hideaki Moteki^{1

2}, Maiko Miyagawa^{1

2}, Shin-Ya Nishio^{1

2}, Shin-Ichi Usami^{1

2}

Affiliations

¹ Department of Otolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
² Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan.

Abstract

Sensorineural hearing loss is one of the most common neurosensory disorders in humans. The incidence of SNHL is estimated to be 1 in 500-1000 newborns. In more than half of these patients, the hearing loss is associated with genetic causes. In Japan, genetic testing for the patients with SNHL using the Invader assay to screen for 46 mutations in 13 deafness genes was approved by the Ministry of Health, Labour and Welfare for inclusion in social health insurance coverage in 2012. Furthermore, from August 2015, this genetic testing has been expanded to screen for 154 mutations in 19 deafness genes using targeted genomic enrichment with massively parallel DNA sequencing combined with the Invader assay and TaqMan genotyping. For this study we analyzed 717 unrelated Japanese hearing loss patients. The total allele frequency of 154 mutations in 19 deafness genes was 32.64% (468/1434) and the total numbers of cases associated with at least one mutation was 44.07% (316/717). Among these, we were able to diagnose 212 (30%) patients, indicating that the present screening could efficiently identify causative mutations in hearing loss patients. It is noteworthy that 27 patients (3.8%) had coexistent multiple mutations in different genes. Five of these 27 patients (0.7%, 5/717 overall) were diagnosed with genetic hearing loss affected by concomitant with responsible mutations in more than two different genes. For patients identified with multiple mutations in different genes, it is necessary to consider that several genes might have an impact on their phenotypes.

MeSH terms

Deafness / genetics*
Humans
Japan
Mutation*
Social Security*

Grants and funding

This study was grant aided by a Health, Labour and Welfare of Japan Scientific Research Grant (H25-Kankaku-Ippan-002), Japan Agency for Medical Research and Development (15dk0310011h0003), and a Grant-in-Aid for Scientific Research (A) (15H02565) from the Ministry of Education, Science and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.