Mutations in mitochondrial DNA (mtDNA) have been identified in some subgroups of mitochondrial encephalomyopathies: a point mutation in diseases with multisystem involvements and a long deletion of various lengths in diseases associated with external ophthalmoplegia. We have identified a point mutation in mitochondrial tRNA-Leu (UUR) gene in a subgroup called MELAS, and found that the protein synthesis in mitochondria was affected in cells where the mutant mtDNA was dominant. The quantitative analyses of the mutant mtDNA in family members of the patients revealed that the mutant mtDNA was maternally inherted and dominantly amplified through generations, although the mechanisms of the dominancy is not known. Also, the quantitation of the mutant mtDNA in one cell by PCR amplification revealed that each cell was heteroplasmy with the wild-type and mutant mtDNA. The accumulated evidences suggest that the major factors that determine the clinical features of mitochondrial diseases are the amount of the mutant mtDNA in cells and the ages of the individuals who has the mutant mtDNAs.
