mtDNA mutations, hearing loss and aminoglycoside treatment in Mexicans

Abstract

St reptomycin 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. Braz J Otorhinolaryngol. 2011;77(5):573-6. ORIGINAL ARTICLE BJORL

Investigation of the A1555G mutation in mitochondrial DNA (MT-RNR1) in groups of Brazilian individuals with nonsyndromic deafness and normal-hearing

“…This mutation occurs in different ethnical groups [Table 1] having among the nonsyndromic deafness the frequencies of: 3% in Japanese,[8] 0.7% in German, 2.4% in Polish,[9] 5.3% in Southeast Asian,[10] 2.4% in Danish. [11] However, it is rare or absent in other groups such as Mexicans[12] and Qatari. [13]…”

Rapid and Accurate Mitochondrial DNA Analysis in Amino Glycoside Sensitive Patients

“…This technique was performed in 3 mitochondrial DNA samples of one normoacusic patient without T1189C mutation and two hypoacusic treated with aminoglycosides formerly selected at the Instituto Nacional de Enfermedades Respiratorias, México and reported earlier [6]. Primers for amplification around the 1189 region were designed on the basis of the sequence reported by Andrews et al [12] corresponding to position 1071-1096 and 1282-1303 (Table 1).…”

“…Primers for amplification around the 1189 region were designed on the basis of the sequence reported by Andrews et al [12] corresponding to position 1071-1096 and 1282-1303 (Table 1). DNA extraction and PCR technique was essentially the same as described in Meza G et al, [6], except that annealing was performed at 55°C for GC-clamp for 30 seconds and final extension for 5 min at 72°C. Purification of amplified fragment and analysis and alignment of sequence were performed in duplicate for each sample as earlier described [6].…”

“…Therefore, we propose the use of a Denaturing Gradient Gel Electrophoresis (DGGE), first described for the use in environmental microbiology to analyze changes in the composition of bacterial populations of 16S rRNA specific nucleotide [5] to determine the presence of the point mutation described earlier by our group (T1189C) in the 12S rRNA mitochondrial gene in individuals with deafness produced by chronic AG treatment [6]. This technique has not been very extensively used in the past in human studies.…”

Frequência da Mutação Mitocondrial C1494T, do Gene MT-RNR1, em Coortes de Ouvintes e Surdos Brasileiros

“…Em outro estudo, na população Espanhola, a mutação C1494T foi confirmada em 17 indivíduos, de três diferentes famílias, em uma amostra de 1.339 sujeitos (1,2 %) 11 . No entanto, a mutação C1494T não foi encontrada em surdos ou ouvintes de outras etnias 16,17,18,19,20 .…”