Aminoglycoside induced ototoxicity associated with mitochondrial DNA mutations

Publication date: Available online 16 June 2016 Source:Egyptian Journal of Medical Human Genetics Author(s): Joseph Foster, Mustafa Tekin Despite the risk of permanent ototoxic effects, aminoglycosides remain commonly utilized antibiotics worldwide due to low cost and efficiency in treating severe infections. Over the last two decades, mitochondrial mutations have been shown to enhance the likelihood of ototoxic injury. In particular the 1555A>G mutation in the mitochondrial gene MTRNR1 has been strongly associated with the onset of aminoglycoside-induced deafness; though pinning down the exact mechanism of action has thus far been elusive. Clinically aminoglycoside-induced deafness has been characterized by variation in the degree of hearing loss, which has prompted an investigation into genetic modifiers. To date, several putative mutations have been categorized as contributing factors to the onset of deafness with no single variation being sufficient to bring about hearing loss. Meanwhile current methods to mitigate the risk of ototoxic injury are in various stages of development. Efforts to alter the molecular structure of aminoglycosides have shown a potential path to reducing ototoxicity while preserving antibacterial properties, but these drugs are not clinically available. On the other hand, application of preemptive audiometry provides the most readily available method to both monitor and reduce the extent of aminoglycoside-induced deafness.
Source: Egyptian Journal of Medical Human Genetics - Category: Genetics & Stem Cells Source Type: research