Analysis of mitochondrial DNA A3243G point mutation in 9 cases with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes

Objective: To study the characteristics of molecular genetics concerning Chinese mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Methods A3243G and T3271C point mutations in the mtDNA of muscle and (or) blood cells were investigated in 9 patients with MELAS and some of their maternal relatives from 7 families by using PCR-RFLP. Furthermore, mutant mtDNA in the sample harboring mutation was quantitatively analysed. Results: The mtDNA A3243G point mutation was unanimously identified in tissues of all patients and 1 of their relatives. However, the T3271C point mutation was identified in none of series in our study. The proportion of mtDNA A3243G was 46.8% - 61.0% in muscle (4 cases) as well as 26.8% - 50.3% in blood (9 cases). In the 3 patients with muscles and blood cells available, their mutant mtDNA proportion in muscle is consistently higher than in blood cells. The study of leukocytes of some maternal relatives from 6 families showed that, while only 1 proband had a sister harboring A3243G mutation and none of the mothers of another 3 probands or siblings of the other 2 probands had the point mutation. However, the sons of 2 probands had not only phenotype of MELAS, but also mtDNA A3243G point mutation in their blood. Conclusion: mtDNA A3243G mutation highly exists in the series with MELAS syndrome in our study and can be detected in various tissues, which is consistent with reports abroad. However, most of our cases are sporadic rather than maternal inherited. It is presumedly caused by a de novo mutation. Whether it is due to ethnic difference or sporadic event needs to be investigated further.