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

• Published in: Journal of the neurological sciences Vol. 320; no. 1; pp. 131 - 135
• Main Authors: Gamba, Juliana, Kiyomoto, Beatriz Hitomi, de Oliveira, Acary Souza Bulle, Gabbai, Alberto Alain, Schmidt, Beny, Tengan, Célia Harumi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-09-2012; Elsevier
• Subjects: Adult; Biological and medical sciences; CPEO; Electron Transport Complex IV - metabolism; Female; Gene polymorphism; Humans; Medical sciences; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial diseases; mtDNA; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Muscle Fibers, Skeletal - metabolism; Mutation; Neurology; Neuromodulation; Ophthalmoplegia; Ophthalmoplegia, Chronic Progressive External - genetics; Ophthalmoplegia, Chronic Progressive External - metabolism; Pathogenicity; Point Mutation - genetics; Polymorphism; RNA, Transfer, Ala - genetics; RNA, Transfer, Lys - genetics; Skeletal muscle; tRNA; Mitochondria; tRNA; mtDNA; CPEO; Mitochondrial diseases; Mutation; Polymorphism; Human; Nervous system diseases; Metabolic diseases; Enzymopathy; Mitochondrial disorder; Genetic disease; Eye disease; Chronic; Ophthalmoplegia; Oculomotor syndrome
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2012.05.037

Abstract We identified a double mutation in a patient with chronic progressive external ophthalmoplegia, located in the tRNAAla (m.5628T>C) and tRNALys (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.