Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to the bacterial 16S ribosomal subunit. They are also associated with adverse events, including aminoglycoside-induced hearing loss (AIHL). Patients who carry certain variants in the MT-RNR1 gene, which encodes the 12S ribosomal subunit, are at a greatly increased risk of developing AIHL. These variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome and inhibiting protein synthesis. This ultimately results in hearing loss due to cell death in the cochlea.
This is the first CPIC guideline on a mitochondrial gene. As the mitochondrial genome is haploid, rather than diploid, recommendations are given for single variants, rather than for combinations of alleles.