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A Novel Mitochondrial DNA Mutation in COX1 Leads to Strokes, Seizures, and Lactic Acidosis

Lookup NU author(s): Dr Mazhor Aldosary, Professor Robert Taylor


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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

Publication metadata

Author(s): Tam EWY, Feigenbaum A, Addis JBL, Blaser S, MacKay N, Al-Dosary M, Taylor RW, Ackerley C, Cameron JM, Robinson BH

Publication type: Article

Publication status: Published

Journal: Neuropediatrics

Year: 2008

Volume: 39

Issue: 6

Pages: 328-334

ISSN (print): 0174-304X

ISSN (electronic): 1439-1899

Publisher: Georg Thieme Verlag


DOI: 10.1055/s-0029-1202287


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