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 heter ogeneity, The mothers of the two families had adult-onset myopathy wit h ragged-red fibers, partial deficiency of cytochrome c oxidase, and s ensory neuropathy. Members of the first family had variable clinical f eatures of progressive ataxic-myoclonic encephalomyopathy and of the o ther family, primarily adult-onset myopathy. There was a point mutatio n from A to G at nucleotide pair 8344 located in the tRNA(Lys) gene of the mtDNA of all patients tested, three in Family 1, and the mother o f Family 2. This clinical heterogeneity may reflect the effects of var ying proportions of mutant and wild-type mtDNA in the different organ systems in each individual.