Pathogenesis of hereditary deafness associated with mitochondrial 12S rRNA 1095 T>C mutation

Objective To investigate the effects of aminoglycosides, nuclear genes, and mitochondrial haplotypes on the phenotype of mitochondrial 1095 TC mutation. Methods Comprehensive history examinations, physical examinations and audiometry were conducted in three pedigrees carrying mitochondrial 1095 TC mutation. The complete mitochondrial genomes and common deafness-related genes, including GJB2, GJB6, GJB3 and SLC26A4, were sequenced in three probands. Results The clinical evaluations revealed that the three probands shared some common features: bilateral and sensorineural hearing impairment. Strikingly, only probands of these pedigrees exhibited severe to profound hearing loss. All of the three probands had the history of using aminoglycosides. Clinical and genetic evaluations revealed extremely low percentage of hearing loss in these Chinese families. A sequence analysis of the complete mitochondrial genomes in three probands showed that the distinct sets of mtDNA polymorphism, in addition to the identical mitochondrial 12S rRNA1095 TC mutation, the 1095 TC mutation was found in one of the 75 Chinese controls. Conclusion The extremely low percentage of hearing loss with the 1095 TC mutation in these genetically unrelated subjects implies that the mitochondrial variants may not play an important role in the phenotypic expression of the 1095 TC mutation in these Chinese families. However, the history of exposure to aminoglycosides in these three hearing-impaired subjects suggests that the aminoglycosides are very likely the cause of hearing loss.