title: Mutations in mtDNA-encoded cytochrome c oxidase subunit genes causing isolated myopathy or severe encephalomyopathy.
abstract: We report on clinical, histological and genetic findings in two patients carrying novel heteroplasmic mutations in the mitochondrial cytochrome c oxidase subunit genes COII and COIII. The first patient, a 35 year-old man had a multisystemic disease, with clinical symptoms of bilateral cataract, sensori-neural hearing loss, myopathy, ataxia, cardiac arrhythmia, depression and short stature and carried a 7970 G>T (E129X) nonsense mutation in COII. A sudden episode of metabolic encephalopathy caused by extremely high blood lactate lead to coma. The second patient developed exercise intolerance and rhabdomyolysis at age 22 years. A heteroplasmic missense mutation 9789 T>C (S195P) was found in skeletal muscle, but not in blood and myoblasts pointing to a sporadic mutation. Our report of two patients with isolated COX deficiency and new mutations in COX subunit genes may help to draw more attention to this type of mtDNA defects and provide new aspects for counselling affected families.
authors.affiliation: Metabolic Disease Center Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics, Academic Hospital Schwabing, Kölner Platz 1, 80804 Munich, Germany. Rita.Horvath@lrz.uni-muenchen.de
authors.forename: R
authors.initials: R
authors.lastname: Horváth
authors.forename: B G H
authors.initials: BG
authors.lastname: Schoser
authors.forename: J
authors.initials: J
authors.lastname: Müller-Höcker
authors.forename: M
authors.initials: M
authors.lastname: Völpel
authors.forename: M
authors.initials: M
authors.lastname: Jaksch
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis / Q000379:methods; D003576:Electron Transport Complex IV / Q000235:genetics*; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D011392:Proline / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012206:Rhabdomyolysis / Q000235:genetics / Q000473:pathology; D012694:Serine / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D018698:Glutamic Acid; D012694:Serine; D011392:Proline; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV