title: Myoclonus epilepsy associated with ragged-red fibers: a G-to-A mutation at nucleotide pair 8363 in mitochondrial tRNA(Lys) in two families.
abstract: 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 tRNA(Lys) coding region are related to the MERRF phenotype and are responsible for the reduced CCO activity.
authors.affiliation: Department of Laboratory Medicine, National Center Hospital for Mental, Nervous and Muscular Disorders, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ozawa
authors.forename: I
authors.initials: I
authors.lastname: Nishino
authors.forename: S
authors.initials: S
authors.lastname: Horai
authors.forename: I
authors.initials: I
authors.lastname: Nonaka
authors.forename: Y I
authors.initials: YI
authors.lastname: Goto
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D017124:Conserved Sequence; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D017243:MERRF Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D012313:RNA / Q000235:genetics; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer
chemical_list: D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012313:RNA; D012343:RNA, Transfer