title: 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: Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.
authors: Juliana
authors: J
authors: Gamba
authors: Beatriz Hitomi
authors: BH
authors: Kiyomoto
authors: Acary Souza Bulle
authors: AS
authors: de Oliveira
authors: Alberto Alain
authors: AA
authors: Gabbai
authors: Beny
authors: B
authors: Schmidt
authors: Célia Harumi
authors: CH
authors: Tengan
mesh_terms: D000328:Adult; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics*; D012344:RNA, Transfer, Ala / Q000235:genetics*; D012357:RNA, Transfer, Lys / Q000235:genetics*
chemical_list: D012344:RNA, Transfer, Ala; D012357:RNA, Transfer, Lys; D003576:Electron Transport Complex IV