A novel mutation (8342G -> A) in the mitochondrial tRNA(Lys) gene associated with progressive external ophthalmoplegia and myoclonus

We describe a patient who suffered from impaired ocular motility from age 1 0 years and at 16 years developed ptosis, proximal weakness and progressive fatigability. At 35 years she developed massive myoclonic jerks, and head and distal tremor. A muscle biopsy showed a high percentage of cytochrome c oxidase negative fibers but no ragged-red fibers. A novel heteroplasmic mu tation (8342G --> A) was found in the mitochondrial transfer RNA(Lys) gene by single-strand conformation polymorphism screening, followed by sequence and restriction fragment length polymorphism analysis. Approximately 80% of muscle mitochondrial DNA (mtDNA) harbored the mutation, while the mutation was absent in lymphocyte DNA of the proband, as well as of her mother, dau ghter and a maternal aunt. However, the pathogenicity of the mutation was c onfirmed by restriction fragment length polymorphism analysis of single mus cle fibers, which revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase negative over cytochrome c oxidase positive fibers. ( C) 1999 Elsevier Science B.V. All rights reserved.