title: Structural analysis of tissues affected by cytochrome C oxidase deficiency due to mutations in the SCO2 gene.
abstract: Structural and histochemical studies carried out in a series of seven cases (from five families) with isolated cytochrome c oxidase (COX) deficiency caused by mutations in the SCO2 gene (1, 2) disclosed changes concentrated in the nervous system, skeletal muscle and myocardium. In five patients homozygous for the E140K mutation, the phenotype was predominantly neuromuscular and the average life span ranged between 9 and 15 months. In two cases, the course was more rapid (death at 7 and 11 weeks of life) and featured marked cardiac hypertrophy (3- and 4-fold increase in heart weight). This predominantly cardiomyopathic phenotype was associated with compound heterozygosity (E140K with another nonsense mutation) in the SCO2 gene. Polioencephalopathy with neurodegeneration and neuronal drop out was present in all cases with evidence that retinal neurons might be seriously affected too. Involvement of spinal motoneurons together with cytochrome c oxidase deficiency in muscle represents a "double hit" for the skeletal muscle. The mitochondrial population was not found to be significantly increased or structurally altered, with the exception of two compound heterozygotes in which the cardiac mitochondria were increased in number and size. Our report extends knowledge of the pathology of COX deficiency caused by mutations in the SCO2 gene.
authors.affiliation: Centre of Applied Genomics, Department of Paediatrics, Charles University and University Hospital, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Vesela
authors.forename: Helena
authors.initials: H
authors.lastname: Hulkova
authors.forename: Hana
authors.initials: H
authors.lastname: Hansikova
authors.forename: Jiri
authors.initials: J
authors.lastname: Zeman
authors.forename: Milan
authors.initials: M
authors.lastname: Elleder
mesh_terms: D006332:Cardiomegaly / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002490:Central Nervous System / Q000473:pathology; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008928:Mitochondria / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics; D018832:Molecular Chaperones; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D009474:Neurons / Q000473:pathology; D035781:Siblings
chemical_list: D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C400285:SCO2 protein, human; D003576:Electron Transport Complex IV