A novel mitochondrial mutation, 1556C --> T, in a Japanese patient with streptomycin-induced tinnitus.
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.


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.
Tanimoto
Hitoshi
H
Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. tanimoto@med.kobe-u.ac.jp
Nishio
Hisahide
H
Matsuo
Masafumi
M
Nibu
Ken-ichi
K
D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001301:Audiometry, Pure-Tone; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012335:RNA, Ribosomal / Q000235:genetics; D017422:Sequence Analysis, DNA; D013307:Streptomycin / Q000009:adverse effects*; D014012:Tinnitus / Q000139:chemically induced* / Q000235:genetics
D000900:Anti-Bacterial Agents; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D013307:Streptomycin