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Published on: March 16, 2018
mtDNA mutations, hearing loss and aminoglycoside treatment in Mexicans
G Meza1, N M Torres-Ruíz, C Tirado-Gutiérrez
1División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. gmeza@ifc.unam.mx
Unlabelled:
Streptomycin and aminoglycoside derivatives are commonly used to treat tuberculosis and other stubborn infections; these drugs may alter auditory and/or vestibular function. Mutations in mitochondrial DNA have been associated with hypersensitivity to aminoglycosides; no studies have been conducted in Mexicans, which are very prone to such alterations because aminoglycosides have been prescribed carelessly for many years, irrespective of the ailment to be treated.
Aim:
We investigated "hot spot" mutations described previously as causing inner ear alterations.
Methods:
Hot spot mutations at the 12S rRNA gene and the tRNA Serine (UCN) gene were screened by PCR-RFLP and sequencing in 65 subjects undergoing audiological and vestibular testing.
Study Design:
Experimental.
Results:
32 individuals had healthy auditory and vestibular function, whereas 33 subjects had auditory affections. We found none of the previously reported mutations related to aminoglycoside hypersensitivity, or non-syndromic hearing loss. Two hearing-impaired patients that had been treated with streptomycin had the T1189C variant of the mitochondrial 12S rRNA region.
Conclusion:
Mutations related to hearing loss in other ethnic backgrounds were not found in Mexicans. However, the T1189C variant is possibly a putative mutation related to aminoglycoside hypersensitivity and was present in 2 patients.
Insights
Aminoglycoside antibiotics can cause hearing loss. In Mexicans, a T1189C mitochondrial variant was found in two patients treated with streptomycin, suggesting it may be linked to hypersensitivity.
Area of Science:
- Genetics
- Otolaryngology
- Pharmacology
Background:
- Streptomycin and aminoglycosides treat tuberculosis but can cause auditory and vestibular dysfunction.
- Mitochondrial DNA mutations are linked to aminoglycoside hypersensitivity.
- Mexicans are susceptible to these alterations due to historical overuse of aminoglycosides.
Purpose of the Study:
- Investigate specific "hot spot" mitochondrial DNA mutations previously linked to inner ear damage.
- Determine the prevalence of these mutations in a Mexican population undergoing audiological and vestibular testing.
Main Methods:
- Screened 65 subjects for mutations in the 12S rRNA and tRNA Serine (UCN) genes using PCR-RFLP and sequencing.
- Conducted audiological and vestibular assessments on all participants.
Main Results:
- 32 subjects had normal auditory and vestibular function; 33 had auditory impairments.
- No previously identified mutations for aminoglycoside hypersensitivity or non-syndromic hearing loss were detected.
- Two hearing-impaired patients treated with streptomycin exhibited the T1189C variant in the mitochondrial 12S rRNA.
Conclusions:
- Commonly reported mutations for hearing loss in other populations were not found in this Mexican cohort.
- The T1189C mitochondrial variant is a potential candidate mutation associated with aminoglycoside hypersensitivity in Mexicans.
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