A MITOCHONDRIAL TRANSFER-RNA ANTICODON SWAP ASSOCIATED WITH A MUSCLE DISEASE

We have identified an unusual mitochondrial (mt) tRNA mutation in a se ven year-old girl with a pure myopathy. This G to A transition at mtDN A position 15990 changed the anticodon normally found in proline tRNAs (UGG) to the one found in serine tRNAs (UGA), and is the first pathog enic anticodon alteration described in a higher eukaryote. The mutant mtDNA was heteroplasmic (85% mutant) in muscle but was undetectable in white blood cells from the patient and her mother. Analysis of single muscle fibres indicated that mutant mtDNAs severely impaired mitochon drial protein synthesis and respiratory chain activity, but only when present at greater than 90%. The recessive behaviour of this mtDNA alt eration may explain the patient's relatively mild clinical phenotype.