難聴の遺伝子診断とその臨床応用

抄録

Congenital hearing loss is one of the most common sensory disorders, with genetic causes accounting for 60–70% of cases. Although recent advances in the identification of deafness genes have resulted in more accurate molecular diagnosis, leading to better determination of suitable clinical interventions, difficulties remain with regard to the clinical application of these interventions, because of the extreme genetic heterogeneity of deafness.

We first applied the Invader assay for screening 46 known mutations of 13 known deafness genes based on the mutation spectrum in Japanese hearing loss patients. The Invader assay based screening enabled us to detect deafness gene mutations in 30% of the patients. In Japan, since 2012, genetic testing using the Invader assay for deafness has been covered by social health insurance.

Toward more effective genetic testing, we adopted next-generation sequencing analysis in order to diagnose common mutations responsible for deafness and discover rare causative gene mutations. Prior to its clinical application, we investigated the accuracy of this genetic testing. We compared the results of invader assay-based genetic screening, the accuracy of which has already been verified in previous studies, with those of next-generation sequencing-based genetic testing in a large population of Japanese deafness patients, which revealed a greater than 99.98% consistency of the results between the two genetic testing methods.