Systematic analysis of mitochondrial genes associated with hearing loss in the Japanese population: dHPLC reveals a new candidate mutation

Abstract

Abstract Background Variants of mitochondrial DNA (mtDNA) have been evaluated for their association with hearing loss. Although ethnic background affects the spectrum of mtDNA variants, systematic mutational analysis of mtDNA in Japanese patients with hearing loss has not been reported. Methods Using denaturing high-performance liquid chromatography combined with direct sequencing and cloning-sequencing, Japanese patients with prelingual (N = 54) or postlingual (N = 80) sensorineural hearing loss not having pathogenic mutations of m.1555A > G and m.3243A > G nor GJB2 were subjected to mutational analysis of mtDNA genes (12S rRNA, tRNA Leu(UUR) , tRNA Ser(UCN) , tRNA Lys , tRNA His , tRNA Ser(AGY) , and tRNA Glu ). Results We discovered 15 variants in 12S rRNA and one homoplasmic m.7501A > G variant in tRNA Ser(UCN) ; no variants were detected in the other genes. Two criteria, namely the low frequency in the controls and the high conservation among animals, selected the m.904C > T and the m.1105T > C variants in 12S rRNA as candidate pathogenic mutations. Alterations in the secondary structures of the two variant transcripts as well as that of m.7501A > G in tRNA Ser(UCN) were predicted. Conclusions The m.904C > T variant was found to be a new candidate mutation associated with hearing loss. The m.1105T > C variant is unlikely to be pathogenic. The pathogenicity of the homoplasmic m.7501T > A variant awaits further study.