The role of complex I genes in MELAS: a novel heteroplasmic mutation 3380G>A in ND1 of mtDNA.

While Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is typically associated with mutations in the mitochondrial tRNA(Leu) gene, mutations in complex I subunit genes of the mtDNA have emerged as a second significant cause. Here we report a novel mutation in the mitochondrial complex I subunit gene ND1 in a patient with late-onset MELAS. The 3380G>A mutation shows very good evidence of pathogenicity as it is heteroplasmic, undetectable in controls, alters a highly conserved amino acid, and is more abundant in ragged-red than in normal muscle fibers. These findings support the significant role of complex I mutations in MELAS.