The mutations m.5628T>C and m.8348A>G in single muscle fibers of a patient with chronic progressive external ophthalmoplegia.

Abstract

We identified a double mutation in a patient with chronic progressive external ophthalmoplegia, located in the tRNA(Ala) (m.5628T>C) and tRNA(Lys) (m.8348A>G) genes. Both mutations were previously described separately and considered pathogenic, however the same mutations were also reported as polymorphisms or phenotype modulator. We analyzed the proportion of each mutation in isolated muscle fibers by single fiber-polymerase chain reaction to investigate the contribution of each mutation to mitochondrial deficiency. Our findings demonstrated that the mutations were heteroplasmic in skeletal muscle and both mutations were present in all single muscle fibers. The proportions of the m.5628T>C mutation were not significantly different between normal and cytochrome-c-oxidase (COX) deficient fibers. However, a significant higher proportion of the m.8348A>G mutation was observed in COX deficient fibers. Homoplasmic m.8348A>G was only observed in COX negative fibers. In conclusion, we provide a piece of evidence toward the pathogenicity of the m.8348A>G mutation and suggest that m.5628T>C is probably a neutral polymorphism.

• Authors: Juliana Gamba, Beatriz Hitomi Kiyomoto, Acary Souza Bulle de Oliveira, Alberto Alain Gabbai, Beny Schmidt, Célia Harumi Tengan
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 320 Issue 1-2 Pg. 131-5 (Sep 15 2012) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 22743145 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• RNA, Transfer, Ala
• RNA, Transfer, Lys
• Electron Transport Complex IV

Topics

• Adult
• Electron Transport Complex IV (metabolism)
• Female
• Humans
• Mitochondria (genetics, metabolism)
• Muscle Fibers, Skeletal (metabolism)
• Ophthalmoplegia, Chronic Progressive External (genetics, metabolism)
• Point Mutation (genetics)
• RNA, Transfer, Ala (genetics)
• RNA, Transfer, Lys (genetics)