Genetic Analysis of Deafness

Hearing loss is an extremely heterogenous disorder, and more than 120 genes are currently considered to be implicated in non-syndromic hearing loss, making the screening strategy difficult. Targeted genome resequencing using massively parallel DNA sequencing (MPS) has become a powerful strategy for the identification of causative genes from among the large numbers of genes in rare Mendelian disorders such as deafness. This sequencing technology followed by an appropriate filtering algorithm will be able to identify rare responsible genes for individual hearing loss patients.

The Department of Hearing Implant Sciences has collaborated with 102 facilities in Japan and collected DNA samples and clinical data from more than 14,000 hearing loss patients. At the same time, international collaborative research on genetic analysis of cochlear implant patients is currently underway. We have received more than 450 samples from 10 HEARRING centers for the analysis of the genetic background of CI/EAS patients.

In 2022, we published study results for the NGS analysis of 10,047 patient samples obtained from social health insurance-based genetic testing of hearing loss using the same platform based on a diagnostic DNA panel carrying 63 deafness genes and the same filtering algorithm (Usami & Nishio Hum. Genet. 2022). This is the world’s largest cohort for NGS analysis of hearing loss to date. The most remarkable result obtained in this comprehensive study was that the data could be used for the first time to clarify genetic epidemiology from congenital/early-onset deafness to late-onset hearing loss. The overall diagnostic rate was 38.8% (Figure 1), with the rate differing for each age group; 48.6% for the congenital/early-onset group (~5 y.o.), 33.5% for the juvenile/young adult-onset group, and 18.0% for the 40+ y.o. group (Figure 2). Interestingly, each group showed a different kind of causative gene.

Figure 1. Responsible genes found in 10,047 hearing loss patients.

Figure 2. Responsible genes in each age group (congenital/6–39 y.o./ over 40 y.o.).

In addition to this comprehensive report, we have published many reports on the detailed clinical information for each gene-associated form of hearing loss (see Publication list). We also undertaking studies on the genetic background for cochlear implant and electrical acoustic stimulation (EAS) patients. We have also reported on cochlear implantation from the perspective of genetic background (Usami et al., Anat Rec. 2020).

Through the genetic analysis of deafness, we would like to clarify the detailed clinical characteristics (onset age, severity, progressiveness, outcome of CI or EAS, etc.) of hearing loss caused by each gene, and would also like to provide useful information regarding future clinical applications, including genetic counseling, selection of appropriate interventions and rehabilitation.