• The Laryngoscope · Apr 2005

    Audiologic testing and molecular analysis of 12S rRNA in patients receiving aminoglycosides.

    • Nicolas Gürtler, Nicolas Schmuziger, Yuil Kim, Anand N Mhatre, Manuel Jungi, and Anil K Lalwani.
    • Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
    • Laryngoscope. 2005 Apr 1; 115 (4): 640-4.

    BackgroundPathogenic mutations in the mitochondrial genome are associated with a wide variety of maternally inherited human diseases including sensorineural hearing loss (HL). A specific mutation, m.1555A>G in the mitochondrial 12S rRNA gene, is associated with predisposition to aminoglycoside ototoxicity and HL. Mutation screening in this gene has been recommended before use of aminoglycosides as a preventative strategy to reduce the risk of ototoxicity.ObjectiveTo study the incidence of mutations in the 12S rRNA gene in patients being treated with aminoglycosides and its correlation with ototoxicity.MethodsPatients undergoing treatment with aminoglycosides were prospectively enrolled in this study (n = 27). Total dosage administered and therapeutic levels of the antibiotic were noted. All patients underwent high-frequency pure-tone audiometry pre- and posttherapy and sequencing of the 12S rRNA gene. In addition, 12S rRNA gene was also sequenced in 50 controls to characterize population specific polymorphisms.ResultsFive of 27 patients suffered from HL involving the high frequencies: four mild and one moderate. Only one of the five patients with ototoxicity harbored two sequence alterations in 12S rRNA of uncertain pathogenicity. The m.1555A>G and m.961delTInsCn mutations were not detected.ConclusionsHigh-frequency pure-tone audiometry is critical for detection of aminoglycoside-induced HL. In the Swiss population, screening for mutations in the 12S rRNA gene, before the initiation of aminoglycoside therapy, is not supported by this limited study. A larger multicenter and multicultural study is warranted to more definitively address this critical clinical issue.

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