A novel mitochondrial tRNALeu(UUR) mutation in a patient with features of MERRF and Kearns-Sayre syndrome

Yutaka Nishigaki, Saba Tadesse, Eduardo Bonilla, Dikoma Shungu, Stephen Hersh, Bronya J.B. Keats, Charles I. Berlin, Morton F. Goldberg, Jerry Vockley, Salvatore DiMauro, Michio Hirano

Research output: Contribution to journalArticlepeer-review


In a patient with clinical features of both myoclonus epilepsy ragged-red fibers (MERRF) and Kearns-Sayre syndrome (KSS), we identified a novel guanine-to-adenine mitochondrial DNA (mtDNA) mutation at nucleotide 3255 (G3255A) of the tRNALeu(UUR) gene. Approximately 5% of the skeletal muscle fibers had excessive mitochondria by succinate dehydrogenase histochemistry while a smaller proportion showed cytochrome c oxidase (COX) deficiency. In skeletal muscle, activities of mitochondrial respiratory chain complexes I, I+III, II+III, and IV were reduced. The G3255A transition was heteroplasmic in all tissues tested: muscle (53%), urine sediment (67%), peripheral leukocytes (22%), and cultured skin fibroblasts (<2%). The mutation was absent in 50 control DNA samples. Single-fiber analysis revealed a higher proportion of mutation in COX-deficient RRF (94%±5, n=25) compared to COX-positive non-RRF (18%±9, n=21). The identification of yet another tRNALeu(UUR) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.

Original languageEnglish (US)
Pages (from-to)334-340
Number of pages7
JournalNeuromuscular Disorders
Issue number4
StatePublished - May 2003


  • Kearns-Sayre syndrome
  • Mitochondrial DNA
  • Mitochondrial encephalomyopathy
  • Myoclonus epilepsy ragged-red fibers
  • Point mutation
  • tRNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


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