Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity

Abstract

Purpose: Aminoglycoside-induced deafness has been described in a number of Chinese pedigrees. In nearly all of these families, affected individuals were related through the maternal side. Because mitochondrial DNA is transmitted exclusively through mothers, it had been speculated that a mutation in the mitochondrial DNA might predispose these maternally related family members to aminoglycoside ototoxicity. Recently, we analyzed three such families with multiple cases of ototoxic deafness and identified a pathogenic mutation in the mitochondrial 12S ribosomal RNA gene at nucleotide position 1555. The purpose of the current study is to analyze individuals with no family history of deafness, who had severe hearing loss after aminoglycoside exposure, for presence or absence of this particular mitochondrial DNA mutation. Materlals and Methods: Blood was obtained from 36 Chinese individuals who became deaf after aminoglycoside exposure and had no family history of deafness. The DNA of these individuals was extracted, amplified by the polmerase chain reaction, and analyzed for the mitochondrial ribosomal RNA gene mutation by allele-specific oligonucleotide hybridization and Southern blot analysis. Results: In one of these 36 sporadic cases, we identified the nucleotide 1555 A→G mutation in the mitochondrial genome. Conclusion: This finding implies that a small proportion of individuals at risk for aminoglycoside ototoxicity harbor the specific mitochondrial DNA mutation identified in the familial cases. In these individuals, a genetic susceptibility to the ototoxic effects of aminoglycosides can be diagnosed, and deafness can be prevented in maternal relatives by avoiding the use of these antibiotics.