title: Deficiency of complex III of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease.
abstract: Facioscapulohumeral disease (FSHD), an inherited neuromuscular disorder, is characterized by progressive wasting of specific muscle groups, particularly the proximal musculature of the upper limbs; the primary defect in this disorder is unknown. We studied a patient with FSHD to determine whether the mitochondrial respiratory chain was functionally abnormal. Muscle biopsy revealed fiber atrophy with patchy staining for oxidative enzymes. Electron microscopy of a liver section showed many enlarged mitochondria with paracrystalline inclusions. Decreased oxidation of the respiratory substrates-alanine and succinate-in skin fibroblasts suggested a deficiency of complex III of the electron-transport chain; cytochrome c oxidase activity (complex IV) was in the normal range. Biochemical analysis of liver supported the fibroblast data, since succinate oxidase activity (electron-transport activity through complexes II-IV) was reduced, whereas complex IV activity was normal. Furthermore, analysis of the cytochrome spectrum in liver revealed typical peaks for cytochromes cc1 and aa3, whereas cytochrome b (a component of complex III) was undetectable. Southern blot analysis of fibroblast mtDNA revealed no major deletions or rearrangements. Our study provides the first documentation of a specific enzyme-complex deficiency associated with FSHD.
authors.affiliation: Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
authors.forename: D M
authors.initials: DM
authors.lastname: Slipetz
authors.forename: J R
authors.initials: JR
authors.lastname: Aprille
authors.forename: P R
authors.initials: PR
authors.lastname: Goodyer
authors.forename: R
authors.initials: R
authors.lastname: Rozen
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D002478:Cells, Cultured; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000032:analysis; D004579:Electron Transport / Q000235:genetics; D014450:Electron Transport Complex III / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000648:ultrastructure; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
chemical_list: D004272:DNA, Mitochondrial; D014450:Electron Transport Complex III