Organ distribution of mutant mitochondrial tRNA(leu(UUR)) gene in a MELAS patient

Abstract

Point mutations in the mitochondrial tRNA(leu(UUR)) gene have been recently reported in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). To investigate the relationship between the degree of heteroplasmy and the organ damage, the ratio of mutant and wildtype genes was quantitated in 14 different organs obtained at an autopsy case of MELAS. The percentages of mitochondrial tRNA(leu(UUR)) gene carrying an A to G transition mutation at nucleotide 3243 were determined by the restriction enzyme digestion of the polymerase chain reaction products. The organs largely depending on oxidative phosphorylation for the sources of energy contained higher proportions of the mutant tRNA(leu(UUR)) gene than organs with a lower oxygen demand. However, the percentage of the mutant genes was similar in both symptomatic and asymptomatic organs with a higher oxygen demand.