OBJECTIVE: Aminoglycoside antibiotics are associated with ototoxicity. The 1555A --> G mutation in the 12S ribosomal RNA gene of mitochondrial DNA has been considered to be associated with susceptibility to aminoglycoside antibiotics. In this study we examined a 79-year-old Japanese patient with a 45-year history of streptomycin-induced tinnitus in an attempt to find a mitochondrial mutation. MATERIALS AND METHODS: DNA was extracted from the patient's leukocytes. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) screening for the 1555A --> G mutation was done in order to detect a mitochondrial mutation and then nucleotide sequencing analysis was performed to identify the mutation. RESULTS: PCR-RFLP screening detected the presence of a mitochondrial mutation in the patient. However, the nucleotide sequencing analysis showed that the mutation was not the 1555A --> G mutation but a novel mutation, 1556C --> T. The mutation was not found in 112 unrelated Japanese control subjects, suggesting that the mutation was specific to our patient. CONCLUSIONS: The 1556C --> T mutation may be a genetic risk factor for aminoglycoside-induced hearing impairment. Our result also suggests that patients with the 1556C --> T mutation exist among those expected to have the 1555A --> G mutation as a result of PCR-RFLP analysis.
OBJECTIVE:Aminoglycoside antibiotics are associated with ototoxicity. The 1555A --> G mutation in the 12S ribosomal RNA gene of mitochondrial DNA has been considered to be associated with susceptibility to aminoglycoside antibiotics. In this study we examined a 79-year-old Japanese patient with a 45-year history of streptomycin-induced tinnitus in an attempt to find a mitochondrial mutation. MATERIALS AND METHODS: DNA was extracted from the patient's leukocytes. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) screening for the 1555A --> G mutation was done in order to detect a mitochondrial mutation and then nucleotide sequencing analysis was performed to identify the mutation. RESULTS: PCR-RFLP screening detected the presence of a mitochondrial mutation in the patient. However, the nucleotide sequencing analysis showed that the mutation was not the 1555A --> G mutation but a novel mutation, 1556C --> T. The mutation was not found in 112 unrelated Japanese control subjects, suggesting that the mutation was specific to our patient. CONCLUSIONS: The 1556C --> T mutation may be a genetic risk factor for aminoglycoside-induced hearing impairment. Our result also suggests that patients with the 1556C --> T mutation exist among those expected to have the 1555A --> G mutation as a result of PCR-RFLP analysis.
Authors: Soraya Bardien; Hannique Human; Tashneem Harris; Gwynneth Hefke; Rene Veikondis; H Simon Schaaf; Lize van der Merwe; John H Greinwald; Johan Fagan; Greetje de Jong Journal: BMC Med Genet Date: 2009-01-13 Impact factor: 2.103
Authors: Igor A Sobenin; Margarita A Sazonova; Anton Y Postnov; Jukka T Salonen; Yuri V Bobryshev; Alexander N Orekhov Journal: PLoS One Date: 2013-07-09 Impact factor: 3.240