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 posit ion 5521 of mitochondrial tRNA(Trp) gene, in association with familial late-onset mitochondrial myopathy. The mutation was detected in muscl e but not in leukocytes from the family's proband. Morphological and b iochemical studies documented a severe defect of muscle cytochrome c o xidase (COX) activity. RFLP analysis of single muscle fibers demonstra ted segregation of higher percentages of mutated genomes in COX-negati ve ragged red fibres compared with normal fibers. A predominant impair ment in synthesis of subunits I and III of complex IV due to their hig hest relative content of tryptophane might explain the greater suscept ibility of complex IV to the pathogenic effect of this mutation. A pro gressive accumulation of mutated genomes in muscle can account for the late onset of symptoms observed in affected members. (C) 1998 Publish ed by Elsevier Science B.V. All rights reserved.