A late-onset mitochondrial myopathy is associated with a novel mitochondrial DNA (mtDNA) point mutation in the tRNA(Trp) gene.
We detected a novel pathogenic mutation, a G-->A transition at position 5521 of mitochondrial tRNA(Trp) gene, in association with familial late-onset mitochondrial myopathy. The mutation was detected in muscle but not in leukocytes from the family's proband. Morphological and biochemical studies documented a severe defect of muscle cytochrome c oxidase (COX) activity. RFLP analysis of single muscle fibers demonstrated segregation of higher percentages of mutated genomes in COX-negative ragged red fibres compared with normal fibers. A predominant impairment in synthesis of subunits I and III of complex IV due to their highest relative content of tryptophane might explain the greater susceptibility of complex IV to the pathogenic effect of this mutation. A progressive accumulation of mutated genomes in muscle can account for the late onset of symptoms observed in affected members.
Silvestri
G
G
Neurological Institute, Catholic University, UILDM, Rome, Italy.
Rana
M
M
DiMuzio
A
A
Uncini
A
A
Tonali
P
P
Servidei
S
S
D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D004576:Electromyography; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012364:RNA, Transfer, Trp / Q000235:genetics*
D004272:DNA, Mitochondrial; D012364:RNA, Transfer, Trp; D003576:Electron Transport Complex IV