A novel mitochondrial DNA mutation in COX1 leads to strokes, seizures, and lactic acidosis
| Autor: | N. MacKay, J. M. Cameron, A. Feigenbaum, J. B. L. Addis, Robert W. Taylor, B. H. Robinson, Mazhor Al-Dosary, Susan Blaser, E. W. Y. Tam, C. Ackerley |
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| Rok vydání: | 2009 |
| Předmět: |
Mitochondrial DNA
Pathology medicine.medical_specialty DNA Mutational Analysis Respiratory chain Mitochondrion DNA Mitochondrial Electron Transport Complex IV medicine MELAS Syndrome Cytochrome c oxidase Humans Histidine Magnesium Child Magnesium ion Alleles Muscle biopsy medicine.diagnostic_test biology business.industry Learning Disabilities General Medicine Cerebral Infarction Sequence Analysis DNA medicine.disease Molecular biology Heteroplasmy Lactic acidosis Pediatrics Perinatology and Child Health biology.protein Acidosis Lactic Female Neurology (clinical) Epilepsy Tonic-Clonic Psychomotor Disorders business |
| Zdroj: | Neuropediatrics. 39(6) |
| ISSN: | 1439-1899 |
| Popis: | Cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain, with subunits originating both from the mitochondrial and nuclear genome. An eleven-year-old female presented initially with a seizure followed two months later with tonic-clonic seizures, weakness and aphasia. MRI of the cerebral hemispheres showed multiple infarcts. Previous history suggested gross and fine motor control deficits with learning difficulties. A muscle biopsy showed a specific decrease of COX staining in all fibres and pleomorphic mitochondria. Respiratory chain studies confirmed an isolated complex IV defect in muscle, whilst fibroblasts showed an initial COX activity below normal which rapidly came up to the normal range on culture. Sequencing of mtDNA revealed an heteroplasmic m.7023G>A mutation in the COX1 gene, with levels of 96% in muscle, 70% in blood and 50% in the initial skin fibroblast culture dropping to 10% in later passages. The mutation was present in a critical region of the COX1 gene, the V374M change being close to the two histidine residues His376 and His378 co-ordinating with the heme a and a (3), and His367 which co-ordinates a magnesium ion. This case highlights that a MELAS-like syndrome can occur with isolated COX deficiency. |
| Databáze: | OpenAIRE |
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