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.
|
| Abstract |
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.
|
|---|---|
| Authors | K M Clark, R W Taylor, M A Johnson, P F Chinnery, Z M Chrzanowska-Lightowlers, R M Andrews, I P Nelson, N W Wood, P J Lamont, M G Hanna, R N Lightowlers, D M Turnbull |
| Journal | American journal of human genetics (Am J Hum Genet) Vol. 64 Issue 5 Pg. 1330-9 (May 1999) ISSN: 0002-9297 [Print] United States |
| PMID | 10205264 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!