Aminoglycoside ototoxicity associated with mitochondrial DNA mutation

OBJECTIVE: To confirm the effect of genetic susceptibility to aminoglycoside ototoxicity. METHOD: Mitochondrial DNA (mtDNA) from 62 members of 9 aminoglycoside induced deafness families was analysed by PCR-Restriction endonuclease digestion. RESULT: The nucleotide 1555A-->G mutation in 12S rRNA gene of mtDNA was identified in 20 members of 5 families. CONCLUSION: These findings indicate that this mutation is a molecular basis for genetic susceptibility to the ototoxic effect of aminoglycosides. The relationship between the audiovestibular changes and genetic susceptibility to aminoglycoside ototoxicity and the pathogenetic mechanism of susceptible deafness are discussed. The possibility that other gene mutations can also predispose to aminoglycoside ototoxicity is proposed.