A NOVEL MITOCHONDRIAL TRNA(PHE) MUTATION INHIBITING ANTICODON STEM FORMATION ASSOCIATED WITH A MUSCLE DISEASE

We have identified a novel mitochondrial (mt) DNA mutation in the tRNA (Phe)-gene in a patient with an isolated mitochondrial myopathy. This T to C transition at position 618 disrupts a strictly conserved base p air within the anticodon stem of tRNA(Phe). Computer analysis showed t hat the affected base pair is essential for anticodon stem formation o f tRNA(Phe). The mutant mtDNA was heteroplasmic in skeletal muscle (95 % mutant) and peripheral blood cells (20% mutant) from the patient but was undetectable in blood cells from his healthy sister, The patient presented with ragged red fibers and reduced activities of complex I a nd complex III in skeletal muscle, The T618C mutation described here i s the second found in this region. Both mutations affect the same base pair of the tRNA(Phe) anticodon stem substantiating the pathogenic na ture of both mutations. (C) 1998 Academic Press.