Mutations in the mitochondrial 12S rRNA gene MT-RNR1 are associated with hearing loss after aminoglycoside exposure and with non-syndromic hearing loss in the absence of aminoglycoside exposure. The aminoglycosides are a class of antibiotics including streptomycin, gentamicin, kanamycin, amikacin, neomycin, and tobramycin. The natural target of aminoglycosides is the bacterial ribosome, which is structurally similar to the mitochondrial ribosome. MT-RNR1 mutations such as A1555G are thought to increase aminoglycoside binding to mitochondrial ribosomes and reduce mitochondrial protein synthesis, resulting in oxidative stress and death of sensitive cochlear hair cells.¹ Other mutations in this gene have been identified in individuals with post-exposure hearing loss.²

Hearing loss following aminoglycoside exposure in MT-RNR1 mutation carriers may be sudden or delayed and varies in severity but is often severe to profound.³ Mutation carriers who are not exposed to aminoglycosides may also develop hearing loss.¹ Specific mutation carrier rates and risk figures for hearing loss with or without aminoglycide exposure are not well established and vary by ethnicity.¹ The variability in onset and penetrance appears to be governed by a threshold model of environmental contributions, the mitochondrial background haplotype, and multiple nuclear modifier genes.¹

Although mutations in MT-RNR1 account for a significant number of cases, aminoglycoside-related hearing loss can also occur sporadically as a result of aminoglycoside ototoxicity, often related to receiving what is generally accepted as a toxic dose.¹  Hearing loss is a well-known side-effect of aminoglycoside therapy in the general population, and patients who test negative for MT-RNR1 mutations still have a risk of hearing loss as a complication of aminoglycoside therapy.