A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency
| Autor: | Alexander Tzagoloff, Agnès Rötig, Antonio Barrientos, Jan-Willem Taanman, Blandine Mehaye, Jürgen Christoph Von Kleist-Retzow, Pierre Rustin, Marina Gorbatyuk, Isabelle Valnot, Arnold Munnich |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Saccharomyces cerevisiae Proteins Nuclear gene DNA Mutational Analysis Cytochrome-c Oxidase Deficiency Locus (genetics) Saccharomyces cerevisiae Biology Polymerase Chain Reaction Electron Transport Complex IV Consanguinity chemistry.chemical_compound Gene mapping Genetics Humans Point Mutation Missense mutation Cytochrome c oxidase Abnormalities Multiple SURF1 Molecular Biology Genetics (clinical) DNA Primers Alkyl and Aryl Transferases Base Sequence Point mutation Chromosome Mapping Membrane Proteins Exons General Medicine Molecular biology Pedigree Heme A Amino Acid Substitution chemistry Child Preschool biology.protein Female Chromosomes Human Pair 17 |
| Zdroj: | Scopus-Elsevier ResearcherID |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/9.8.1245 |
| Popis: | Cytochrome c oxidase (COX) defects are found in a clinically and genetically heterogeneous group of mitochondrial disorders. To date, mutations in only two nuclear genes causing COX deficiency have been described. We report here a genetic linkage study of a consanguineous family with an isolated COX defect and subsequent identification of a mutation in a third nuclear gene causing a deficiency of the enzyme. A genome-wide search for homozygosity allowed us to map the disease gene to chromosome 17p13.1-q11.1 (Z (max)= 2.46; theta = 0.00 at the locus D17S799). This region encompasses two genes, SCO1 and COX10, encoding proteins involved in COX assembly. Mutation analysis followed by a complementation study in yeast permitted us to ascribe the COX deficiency to a homozygous missense mutation in the COX10 gene. This gene encodes heme A:farnesyltransferase, which catalyzes the first step in the conversion of protoheme to the heme A prosthetic groups of the enzyme. All three nuclear genes now linked to isolated COX deficiency are involved in the maturation and assembly of COX, emphasizing the major role of such genes in COX pathology. |
| Databáze: | OpenAIRE |
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