Phenotypic heterogeneity in families with the myoclonic epilepsy and ragged-red fiber disease point mutation in mitochondrial DNA.

Two families with a point mutation in mtDNA associated with myoclonic epilepsy and ragged-red fiber disease showed pronounced clinical heterogeneity. The mothers of the two families had adult-onset myopathy with ragged-red fibers, partial deficiency of cytochrome c oxidase, and sensory neuropathy. Members of the first family had variable clinical features of progressive ataxic-myoclonic encephalomyopathy and of the other family, primarily adult-onset myopathy. There was a point mutation from A to G at nucleotide pair 8344 located in the tRNALys gene of the mtDNA of all patients tested, three in Family 1, and the mother of Family 2. This clinical heterogeneity may reflect the effects of varying proportions of mutant and wild-type mtDNA in the different organ systems in each individual.