Clinical application of a custom AmpliSeq library and ion torrent PGM sequencing to comprehensive mutation screening for deafness genes

Toward more effective genetic testing, we adopted Massively Parallel DNA Sequencing (MPS) of target genes using an Ion PGM™ system and an Ion AmpliSeq™ panel to diagnose common mutations responsible for deafness and discover rare causative gene mutations. Before its clinical application, we investigated the accuracy of MPS-based genetic testing.

Congenital hearing loss is one of the most common sensory disorders, with 50-70% of cases attributable to genetic causes. Although recent advances in the identification of deafness genes have resulted in more accurate molecular diagnosis, leading to the better determination of suitable clinical interventions, difficulties remain with regard to clinical applications due to the extreme genetic heterogeneity of deafness.

The Ion Personal Genome Machine system had sufficient uniformity and accuracy for application to the clinical diagnosis of common causative mutations and efficiently identified rare causative mutations and/or mutation candidates.

We compared the results of Invader assay-based genetic screening, the accuracy of which has already been verified in previous studies, with those of MPS-based genetic testing for a large population of Japanese deafness patients and revealed that over 99.98% of the results were the same for each genetic testing system.