Novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients

We identified a novel heteroplasmic mutation in the mitochodrial DNA gene e ncoding the ND5 subunit of complex I. This mutation (13514A-->G) hits the s ame codon affected by a previously reported mitochondrial encephalomyopathy , lactic acidosis, and strokelike episodes (MELAS)-associated mutation (135 13G-->A), but the amino acid replacement is different (D393G vs D393N). The 13514A-->G mutation was found in two unrelated MELAS-like patients. Howeve r, in contrast to typical MELAS, lactic acidosis was absent or mild and the muscle biopsy was morphologically normal. Strongly positive correlation be tween the percentage of heteroplasmy and defective activity of complex I wa s found in cybrids, We found an additional 13513G-->A-positive case, affect ed by a progressive mitochondrial encephalomyopathy. Our results clearly de monstrate that the amino acid position D393 is crucial for the function of complex I. Search for D393 mutations should be pare of the routine screenin g for mitochondrial disorders.