A novel heteroplasmic mutation in mitochondrial tRNA^Arg gene associated with non-dystrophic myotonias

Non-dystrophic myotonias (NDM) are rare diseases caused by defects in skeletal muscle chloride and sodium ion channels. It is well established that high-energy consuming tissues such as muscular and nervous systems are exclusively dependent on the ATP generation by mitochondria. The mitochondrial dysfunction, which is caused by mitochondrial DNA mutations, played an important role in the pathogenesis of non-dystrophic myotonias. The purpose of this study is to identify mitochondrial tRNA mutations in non-dystrophic myotonias patients. In this study, 45 Iranian patients with non-dystrophic myotonia were investigated for intracellular ATP content and the mutation screening in all the mitochondrial tRNA genes by DNA sequencing. Our findings showed that lymphocyte intracellular ATP is significantly decreased in NDM patients compared with control subjects (p = 0.001). We found nine mutations in mitochondrial tRNA genes, including m.4454 T > C (in the TψC loop of tRNA^Met), m.5568 A > G (tRNA^Trp), m.5794 T > C (in the anticodon loop of tRNA^Cys), novel m.10438 A > T, and m.10462 T > C (in anticodon loop and ACC stem of tRNA^Arg), m.12308 A > G (tRNA^Leu(CUN)) and m.15907 A > G, m.15924 A > G, and m.15928 G > A (in the anticodon stem of tRNA^Thr) in 31 NDM patients. These results suggest that novel m.10438 A > T mutation is involved in NDM patients and reinforces the significant association between this mutation in mitochondrial tRNA^Arg Gene and NDM patients (p = 0.008).