Clinical, biochemical and molecular analyses of six patients with isolated cytochrome c oxidase deficiency due to mutations in the SCO2 gene
Language English Country Norway Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Electrophoresis, Gel, Two-Dimensional MeSH
- Cytochrome-c Oxidase Deficiency genetics MeSH
- Child MeSH
- Electron Transport Chain Complex Proteins analysis MeSH
- Cardiomyopathy, Hypertrophic genetics MeSH
- Humans MeSH
- Mitochondrial Proteins MeSH
- Mitochondria chemistry MeSH
- Molecular Chaperones MeSH
- Mutation MeSH
- Brain Diseases genetics MeSH
- Proteins genetics MeSH
- Carrier Proteins MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Electron Transport Chain Complex Proteins MeSH
- Mitochondrial Proteins MeSH
- Molecular Chaperones MeSH
- Proteins MeSH
- SCO2 protein, human MeSH Browser
- Carrier Proteins MeSH
BACKGROUND AND AIM: Cytochrome c oxidase (COX) deficiency represents a heterogeneous group of disorders. Numerous proteins are required for efficient COX assembly and maintenance. In 26 children with isolated COX deficiency, we studied mutations in the SCO2 gene, which is involved in the copper transport into the inner mitochondrial membrane, and we analysed the clinical and biochemical consequences of SCO2 mutations. METHODS: The activities of respiratory chain complexes were measured spectrophotometrically in isolated mitochondria and/or crude cell extracts in all available tissues. Two-dimensional polyacrylamide electrophoresis (2D-PAGE) was used to separate the complexes and their subunits. The mutations were detected by sequencing and RFLP analysis. RESULTS: Mutations in the SCO2 gene were found in six children. Early neonatal onset of hypertrophic cardiomyopathy and encephalopathy were observed in one boy with compound heterozygous mutations C1280T and G1541A. In all five children with homozygous mutation G1541A, progressive encephalopathy developed between 2 and 6 mo of age. Isolated COX deficiency was found in the skeletal muscle, heart, liver and brain but not in fibroblasts. 2D-PAGE in the skeletal muscle showed markedly decreased amounts of all COX subunits. CONCLUSION: Our results suggest that mutations in the SCO2 gene are not rare, at least in our population. Although clinical symptoms may rely on the type of SCO2 mutation, the prognosis is unfavourable in all patients.
References provided by Crossref.org
Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1
