title: A novel mutation in the mitochondrial tRNA(Val) gene associated with a complex neurological presentation.
abstract: We describe a patient who presented with progressive ataxia, seizures, mental deterioration, mild myopathy, and hearing loss. A novel heteroplasmic G-to-A transition was found, affecting the acceptor stem of the mitochondrial (mt) tRNA(Val) gene. Mutant mtDNA was 67% of total mtDNA in the muscle of the proband and was also present at low levels in the muscle of his healthy mother. It was absent in all of the numerous control DNA samples that were tested. Analysis of single muscle fibers revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase-negative fibers. Mutations of mtDNA may be responsible of neurological syndromes that, like the case reported here, are clinically puzzling, and lack typical "mitochondrial" clues, such as elevated levels of blood lactate, overt defects of the respiratory complexes, and clinically documented maternal inheritance.
authors.affiliation: Division of Biochemistry and Genetics, National Neurological Institute-IRCCS C. Besta, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Tiranti
authors.forename: L
authors.initials: L
authors.lastname: D'Agruma
authors.forename: D
authors.initials: D
authors.lastname: Pareyson
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: F
authors.initials: F
authors.lastname: Carrara
authors.forename: L
authors.initials: L
authors.lastname: Zelante
authors.forename: P
authors.initials: P
authors.lastname: Gasparini
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D001483:Base Sequence; D030401:Cytochrome-c Oxidase Deficiency; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D006311:Hearing Disorders / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012366:RNA, Transfer, Val / Q000235:genetics*; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012366:RNA, Transfer, Val; D012313:RNA