title: A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome.
abstract: In a patient with clinical features of both myoclonus epilepsy ragged-red fibers (MERRF) and Kearns-Sayre syndrome (KSS), we identified a novel guanine-to-adenine mitochondrial DNA (mtDNA) mutation at nucleotide 3255 (G3255A) of the tRNA(Leu(UUR)) gene. Approximately 5% of the skeletal muscle fibers had excessive mitochondria by succinate dehydrogenase histochemistry while a smaller proportion showed cytochrome c oxidase (COX) deficiency. In skeletal muscle, activities of mitochondrial respiratory chain complexes I, I + III, II + III, and IV were reduced. The G3255A transition was heteroplasmic in all tissues tested: muscle (53%), urine sediment (67%), peripheral leukocytes (22%), and cultured skin fibroblasts (< 2%). The mutation was absent in 50 control DNA samples. Single-fiber analysis revealed a higher proportion of mutation in COX-deficient RRF (94% +/- 5, n = 25) compared to COX-positive non-RRF (18% +/- 9, n = 21). The identification of yet another tRNA(Leu(UUR)) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeon, 630 West 168th Street, P&S 4-443, New York, NY 10032, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishigaki
authors.forename: Saba
authors.initials: S
authors.lastname: Tadesse
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Dikoma
authors.initials: D
authors.lastname: Shungu
authors.forename: Stephen
authors.initials: S
authors.lastname: Hersh
authors.forename: Bronya J B
authors.initials: BJ
authors.lastname: Keats
authors.forename: Charles I
authors.initials: CI
authors.lastname: Berlin
authors.forename: Morton F
authors.initials: MF
authors.lastname: Goldberg
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D000225:Adenine / Q000378:metabolism; D000328:Adult; D000818:Animals; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D006147:Guanine / Q000378:metabolism; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics*; D017243:MERRF Syndrome / Q000235:genetics*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu; D006147:Guanine; D012313:RNA; D003576:Electron Transport Complex IV; D000225:Adenine