title: MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle.
abstract: Disorders of mitochondrial DNA (mtDNA) maintenance are clinically and genetically heterogeneous, embracing recessive mtDNA depletion syndromes affecting children and adult-onset multiple mtDNA deletion disorders. Here we show that mutation of MPV17 - a gene implicated in severe, infantile hepatocerebral mtDNA depletion disorders characterised by a loss of mtDNA copies - can also cause clonally-expanded mtDNA deletion and focal cytochrome c oxidase (COX) deficiency in skeletal muscle associated with an adult presentation of neuropathy and leukoencephalopathy. The mpv17 protein is therefore intimately involved in both the mtDNA replication and repair processes and associated with both quantitative and qualitative mtDNA abnormalities.
authors.affiliation: Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.forename: Anna
authors.initials: A
authors.lastname: Butterworth
authors.forename: Robert D M
authors.initials: RD
authors.lastname: Hadden
authors.forename: Istvan
authors.initials: I
authors.lastname: Bodi
authors.forename: Langping
authors.initials: L
authors.lastname: He
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics*; D011115:Polyneuropathies / Q000150:complications / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C530370:MPV17 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins