THE 8,344-MUTATION IN MITOCHONDRIAL-DNA - A COMPARISON BETWEEN THE PROPORTION OF MUTANT-DNA AND CLINICOPATHOLOGICAL FINDINGS

Ten patients, two men and eight women with mitochondrial encephalomyop athy, had an A-G mutation at nucleotide pair 8,344 in the mitochondria l DNA, the most common genetic defect in myoclonus epilepsy with ragge d-red fibers (MERRF). Eight patients had the clinical and pathologic c haracteristics of MERRF including myoclonus, seizures, cerebellar atax ia and myopathy with ragged-red fibers. Two patients had atypical symp toms such as early onset of fatal cardiac failure and late onset of ra pid mental deterioration, respectively. The striking feature in our pa tients with the 8,344 mutation was that four of 10 patients had cardia c involvement and two developed progressive heart failure. In the typi cal MERRF patients, the proportion of mutant mitochondrial DNA in thei r skeletal muscles, quantified by a single strand conformation polymor phism analysis, was above 85%, However, there was no significant corre lation between clinical severity, histopathological findings and the p roportion of mutant mtDNA in muscle biopsy samples, suggesting that no n-ragged-red fibers play an important role in the phenotypic expressio n of the mutants.