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Lookup NU author(s): Kim Clark, Professor Robert TaylorORCiD, Dr Margaret Johnson, Professor Patrick Chinnery, Emerita Professor Zofia Chrzanowska-LightowlersORCiD, Dr Richard Andrews, Emeritus 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.
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
URL: http://dx.doi.org/10.1086/302361
DOI: 10.1086/302361
PubMed id: 10205264
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