Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a genetically heterogeneous disorder. The most prevalent mitochondrial DNA (mtDNA) mutation associated with MELAS is the m.3243A>G transition in the mitochondrial tRNALeu(UUR) gene. Here, we report the clinical, genetic and molecular characterization of six probands from Han Chinese families with MELAS. Four of six probands carried the heteroplasmic m.3243A>G mutation. The levels of mutation load ranged from 29% to 59%, which were correlated with the severity of the clinical phenotypes. Two probands with MELAS/Leigh overlap were 3243 A>G negative, whose severity and relapse were greater than the other 4 probands. One proband with MELAS/Leigh harbored the known ND5 m.13094T>C mutation, which is related to MELAS/Leigh overlap and cerebella ataxia. Sequence analysis of entire mtDNA showed the distinct sets of variants including some variants that may be associated with diabetes, hearing loss, seizures, cardiomyopathy, and Leigh syndrome. Our data suggested that the phenotype and severity of MELAS mainly depend on the mutation load, and some variants may partially contribute to the phenotype and diversity. Our finding also highlighted the complexity of the relationship between genotype and phenotype in MELAS.
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