Congenital or late-onset myopathy in patients with the T14709C mtDNA mutation.
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.
Mancuso
Michelangelo
M
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Ferraris
Silvio
S
Nishigaki
Yutaka
Y
Azan
Gaetano
G
Mauro
Alessandro
A
Sammarco
Piero
P
Krishna
Sindu
S
Tay
Stacey K H
SK
Bonilla
Eduardo
E
Romansky
Stephen G
SG
Hirano
Michio
M
DiMauro
Salvatore
S
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
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