BACKGROUND: Pathogenic 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. OBJECTIVE: To study the incidence of mutations in the 12S rRNA gene in patients being treated with aminoglycosides and its correlation with ototoxicity. METHODS: Patients 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. RESULTS: Five 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. CONCLUSIONS: High-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.
BACKGROUND: Pathogenic 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 aminoglycosideototoxicity and HL. Mutation screening in this gene has been recommended before use of aminoglycosides as a preventative strategy to reduce the risk of ototoxicity. OBJECTIVE: To study the incidence of mutations in the 12S rRNA gene in patients being treated with aminoglycosides and its correlation with ototoxicity. METHODS:Patients 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. RESULTS: Five 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. CONCLUSIONS: High-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.
Authors: Angela C Garinis; Campbell P Cross; Priya Srikanth; Kelly Carroll; M Patrick Feeney; Douglas H Keefe; Lisa L Hunter; Daniel B Putterman; David M Cohen; Jeffrey A Gold; Peter S Steyger Journal: J Cyst Fibros Date: 2017-02-24 Impact factor: 5.482
Authors: Campbell P Cross; Selena Liao; Zachary D Urdang; Priya Srikanth; Angela C Garinis; Peter S Steyger Journal: Int J Pediatr Otorhinolaryngol Date: 2015-09-09 Impact factor: 1.675
Authors: Valeria Guaran; Laura Astolfi; Alessandro Castiglione; Edi Simoni; Elena Olivetto; Marco Galasso; Patrizia Trevisi; Micol Busi; Stefano Volinia; Alessandro Martini Journal: Int J Mol Med Date: 2013-08-16 Impact factor: 4.101