Sporadic mitochondrial myopathy due to a new mutation in the mitochondrial tRNASer(UCN) gene

We describe a young woman with a progressive mitochondrial myopathy that started with muscle weakness and went on to include deafness, dementia and ataxia. Skeletal muscle showed the histological and biochemical features of mitochondrial respiratory chain dysfunction. Genetic analysis identified a novel, heteroplasmic, A to G transition in tRNA(Ser(UCN)) at position 7480 affecting a highly conserved base in the anticodon loop. Single-fibre PCR showed highest levels of mutation in cytochrome c-oxidase-deficient fibres and quantification in two biopsies taken 5 years apart showed no change in percentage heteroplasmy. The mutation was present at lower levels in the patient's blood, but was not found in either her mother's or sister's blood and skeletal muscle, suggesting a sporadic occurrence. This is the eighth disease-causing mutation in this tRNA gene and confirms serine (UCN) as one of the most common sites for mtDNA mutation.