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An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy

Lookup NU author(s): Kim Clark, Professor Robert Taylor, Dr Margaret Johnson, Professor Patrick Chinnery, Professor Zofia Chrzanowska-LightowlersORCiD, Dr Richard Andrews, Professor Robert Lightowlers, Emeritus Professor Doug Turnbull


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A novel heteroplasmic 7587T→C mutation in the mitochondrial genome which changes the initiation codon of the gene encoding cytochrome c oxidase subunit II (COX II), was found in a family with mitochondrial disease. This T→C transition is predicted to change the initiating methionine to threonine. The mutation load was present at 67% in muscle from the index case and at 91% in muscle from the patient's clinically affected son. Muscle biopsy samples revealed isolated COX deficiency and mitochondrial proliferation. Single-muscle-fiber analysis revealed that the 7587C copy was at much higher load in COX-negative fibers than in COX-positive fibers. After microphotometric enzyme analysis, the mutation was shown to cause a decrease in COX activity when the mutant load was >55%-65%. In fibroblasts from one family member, which contained >95% mutated mtDNA, there was no detectable synthesis or any steady-state level of COX II. This new mutation constitutes a new mechanism by which mtDNA mutations can cause disease-defective initiation of translation.

Publication metadata

Author(s): Clark KM, Taylor RW, Johnson MA, Chinnery PF, Chrzanowska-Lightowlers ZMA, Andrews RM, Nelson IP, Wood NW, Lamont PJ, Hanna MG, Lightowlers RN, Turnbull DM

Publication type: Article

Publication status: Published

Journal: American Journal of Human Genetics

Year: 1999

Volume: 64

Issue: 5

Pages: 1330-1339

Print publication date: 01/05/1999

ISSN (print): 0002-9297

ISSN (electronic): 1537-6605

Publisher: Cell Press


DOI: 10.1086/302361

PubMed id: 10205264


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