Myoclonus epilepsy associated with ragged-red fibers: A G-to-A mutation at nucleotide pair 8363 in mitochondrial tRNALys in two families

In addition to well-known mutations at nucleotide pair 8344 and 8356 in mitochondrial DNA in patients with myoclonus epilepsy associated with ragged-red fibers (MERRF), we found a new G-to-A point mutation at nucleotide 8363 in two Japanese families. The probands had the typical clinical characteristics of MERRF. Since the 8363 mutation was present in a heteroplasmic state, and seen in none of 92 patients with other mitochondrial diseases or 50 normal individuals, this mutation is thought to be disease-related and probably specific to MERRF. As seen in muscle biopsies with the previous two mutations, focal cytochrome c oxidase (CCO) deficiency was the most characteristic finding. With single fiber analysis, the CCO-negative fibers contained a higher percentage of mutant DNA (88.4 ± 6.6%) than CCO-positive fibers (65.1 ± 8.0%). These findings suggest that mutations in tRNALys coding region are related to the MERRF phenotype and are responsible for the reduced CCO activity. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 271–278, 1997.