Molecular diagnosis of deafness

Despite advances in discovery of deafness genes, clinical application still entails difficulties because of the genetic heterogeneity of deafness. In order to establish strategy for clinical application, we reviewed the genes responsible for hearing loss patients in Japan (Usami S et al; Acta Otolaryngol 128: 446-454, 2008), and discussed diagnostic strategy for mutation screening based on a mutation/gene database (Abe S et al; Genet Test 11: 333-340, 2007). Our series of mutation screenings has revealed that mutations in GJB2, SLC26A4, and CDH23, and the 1555A>G mutation in the mitochondrial 12S rRNA, were the major causes of hearing loss in Japanese patients. Interestingly, spectrums of GJB2, SLC26A4, and CDH23 mutations found in the Japanese population were quite different from those reported in populations with European ancestry. Our simultaneous screening of the multiple deafness mutations was based on the mutation spectrum of a corresponding population. The multicenter trial for this assay using an Invader panel revealed that approximately 40% of congenital hearing loss subjects could be diagnosed. This assay will enable us to detect deafness mutations in an efficient and practical manner in the clinical platform.