title: Mitochondrial DNA mutation underlying Leigh's syndrome: clinical, pathological, biochemical, and genetic studies of a patient presenting with progressive myoclonic epilepsy.
abstract: An 18-year-old male patient presented with clinical and radiological evidence of Leigh's syndrome (LS), having developed progressive myoclonic epilepsy and ataxia 11 years previously. Muscle biopsy showed cytochrome oxidase deficiency but no ragged red fibres. Autopsy confirmed the diagnosis of LS; there was additional degenerative change in the cerebellum and dentate and olivary nuclei, and an axonal peripheral neuropathy. Biochemical studies showed reduced activity of complexes I and IV of the respiratory chain in mitochondria from heart, liver and kidney. The mutation of mitochondrial DNA (mtDNA) at position 8344, commonly associated with the syndrome of myoclonic epilepsy and ragged red fibres, was detected in the patient's blood and was present in muscle, brain, liver, heart, and kidney in uniformly high amounts. It is clear that LS is genetically heterogeneous and represents one of the most severe phenotypes of a number of different mtDNA defects.
authors.affiliation: Department of Clinical Neurology, Institute of Neurology, London, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Sweeney
authors.forename: S R
authors.initials: SR
authors.lastname: Hammans
authors.forename: L W
authors.initials: LW
authors.lastname: Duchen
authors.forename: J M
authors.initials: JM
authors.lastname: Cooper
authors.forename: A H
authors.initials: AH
authors.lastname: Schapira
authors.forename: C R
authors.initials: CR
authors.lastname: Kennedy
authors.forename: J M
authors.initials: JM
authors.lastname: Jacobs
authors.forename: B D
authors.initials: BD
authors.lastname: Youl
authors.forename: J A
authors.initials: JA
authors.lastname: Morgan-Hughes
authors.forename: A E
authors.initials: AE
authors.lastname: Harding
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000150:complications*; D006801:Humans; D007888:Leigh Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial