We identified a novel heteroplasmic mutation in the mitochodrial DNA gene encoding the ND5 subunit of complex I. This mutation (13514A→G) hits the same codon affected by a previously reported mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS)-associated mutation (13513G→A), but the amino acid replacement is different (D393G vs D393N). The 13514A→G mutation was found in two unrelated MELAS-like patients. However, in contrast to typical MELAS, lactic acidosis was absent or mild and the muscle biopsy was morphologically normal. Strongly positive correlation between the percentage of heteroplasmy and defective activity of complex I was found in cybrids. We found an additional 13513G→A-positive case, affected by a progressive mitochondrial encephalomyopathy. Our results clearly demonstrate that the amino acid position D393 is crucial for the function of complex I. Search for D393 mutations should be part of the routine screening for mitochondrial disorders.
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