MYOCLONUS EPILEPSY ASSOCIATED WITH RAGGED-RED FIBERS - A G-TO-A MUTATION AT NUCLEOTIDE PAIR-8363 IN MITOCHONDRIAL TRNA(LYS) IN 2 FAMILIES

In addition to well-known mutations at nucleotide pair 8344 and 8356 i n mitochondrial DNA in patients with myoclonus epilepsy associated wit h ragged-red fibers (MERRF), we found a new G-to-A point mutation at n ucleotide 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 thou ght to be disease-related and probably specific to MERRF. As seen in m uscle biopsies with the previous two mutations, focal cytochrome c oxi dase (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 tRNA(Lys) coding region ar e related to the MERRF phenotype and are responsible for the reduced C CO activity. (C) 1997 John Wiley & Sons, Inc.