title: Congenital or late-onset myopathy in patients with the T14709C mtDNA mutation.
abstract: Three patients with different clinical phenotypes harbored the same point mutation at nucleotide 14709 (T14709C) in the tRNAGlu gene of mitochondrial DNA (mtDNA). The first patient was a 21-month-old child with severe congenital myopathy, respiratory distress and mild mental retardation. Muscle biopsy showed about 12% cytochrome c oxidase (COX)-negative ragged-red fibers (RRFs), and markedly decreased activities of mitochondrial respiratory chain complexes I, III and IV. The other two patients were 51- and 55-year-old siblings with slowly progressive myopathy and diabetes mellitus. Muscle biopsy showed focal COX-negative RRFs and decreased activities of complexes I, III and IV. In all three patients, the T14709C mutation was abundant in muscle but present at lower levels in accessible tissues. Previously described patients with the same mutation also showed congenital or late-onset myopathy. Diabetes is frequently associated with both phenotypes and is a clinical clue to the molecular diagnosis.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Silvio
authors.initials: S
authors.lastname: Ferraris
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishigaki
authors.forename: Gaetano
authors.initials: G
authors.lastname: Azan
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mauro
authors.forename: Piero
authors.initials: P
authors.lastname: Sammarco
authors.forename: Sindu
authors.initials: S
authors.lastname: Krishna
authors.forename: Stacey K H
authors.initials: SK
authors.lastname: Tay
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Romansky
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D003545:Cysteine / Q000235:genetics; D030401:Cytochrome-c Oxidase Deficiency; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics*; D048909:Diabetes Complications / Q000150:complications / Q000235:genetics; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000150:complications / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D012343:RNA, Transfer / Q000235:genetics; D013912:Threonine / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D013912:Threonine; D012343:RNA, Transfer; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D003545:Cysteine