title: A novel sporadic mutation in cytochrome c oxidase subunit II as a cause of rhabdomyolysis.
abstract: Disorders of the mitochondrial genome are an important cause of neurological disease, with patients presenting a variety of different phenotypes. Exercise induced muscle pain and myoglobinuria have been described with a number of metabolic defects, but because of the enormous variability of the mitochondrial genome identifying causative mitochondrial DNA mutations can be extremely difficult. Since mitochondrial tRNA genes were considered to be hot spots for mutation, sequencing was initially often confined to these genes. In a patient with symptoms and signs of exercise intolerance and myoglobinuria we originally ascribed pathogenicity to a mitochondrial-tRNA(Phe) mutation but here we show that the true pathogenic mutation was a novel mutation in the gene encoding subunit II of cytochrome c oxidase. We believe that this study demonstrates the importance of whole mitochondrial genome sequencing and of access to large sequence databases.
authors.affiliation: Mitochondrial Research Group, Department of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Framlington Place, NE2 4HH, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Neil
authors.initials: N
authors.lastname: Howell
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D005820:Genetic Testing; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D012206:Rhabdomyolysis / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004272:DNA, Mitochondrial; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV