A mutation in mitochondrial 12S rRNA, A827G, in Argentinean family with hearing loss after aminoglycoside treatment

Abstract

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report the clinical, genetic, and molecular characterization of one Argentinean family with aminoglycoside-induced impairment in two of their members. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects. Mutational analysis of the mtDNA in these pedigrees showed the presence of homoplasmic 12S rRNA A827G mutation, which has been associated with hearing impairment. The A827G mutation is located at the A-site of the mitochondrial 12S rRNA gene which is highly conserved in mammals. It is possible that the alteration of the tertiary or quaternary structure of this rRNA by the A827G mutation may lead to mitochondrial dysfunction, thereby playing a role in the pathogenesis of hearing loss and aminoglycoside hypersensitivity. However, incomplete penetrance of hearing impairment indicates that the A827G mutation itself is not sufficient to produce clinical phenotype.