Detection of A3243G point mutation in mitochondrial DNA from 10 cases of MELAS

Objective To search for A3243G point mutations in mitochondrial DNA (mtDNA) from 10 cases of mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS). Methods Using PCR-restriction analysis, we investigated A3243G point mutations in mtDNA of muscle and/or blood cells from 10 patients and their 8 maternal relatives. We also quantitated the A3243G mtDNA in samples harboring the mutation. Results A3243G point mutations were identified in all muscle and/or blood samples from 10 MELAS patients. The proportion of mutant mtDNA was 10.8% - 47.8% in blood (7 cases), and 39.4% - 67.7% in muscle (5 cases). This ratio was invariably higher in muscle than in blood from two patients whose blood and muscle samples were both available. Younger patients usually carried higher proportions of A3243G mutant mtDNA in blood. Eight maternal relatives from 6 families were also examined. Maternal transmission of the disease could be identified in one family. No A3243G point mutations were found in mothers' blood from 3 families and siblings' blood from 2 families. Conclusions All 10 MELAS patients were found to have the mtDNA A3243G mutation in their muscle and/or blood. The A3243G mutation seems to be sporadic in 5 of the families examined, suggesting the mechanism of de novo mutation for the pathogenesis of their MELAS syndrome.