A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO)

Neuromuscul Disord. 2010 Mar;20(3):204-6. doi: 10.1016/j.nmd.2010.01.006. Epub 2010 Feb 10.

Abstract

We describe a 62-year-old woman with chronic progressive external ophthalmoplegia (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNA(Ile) gene (MTTI). This is the first mutation at position 44 in the variable loop (V loop) of any mitochondrial tRNA. The muscle biopsy revealed 10% ragged-red/ragged-blue fibers and 25% cytochrome c oxidase (COX)-deficient fibers. No deletions or duplications were detected by Southern blot analysis. The 4302A>G transition was present only in the patient's muscle and single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient than in normal fibers. Like tRNA(Leu(UUR)), tRNA(Ile) appears to be a "hot spot" for mtDNA mutations causing CPEO.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / metabolism
  • Female
  • Humans
  • Middle Aged
  • Muscle Fibers, Skeletal / pathology
  • Mutation / genetics*
  • Ophthalmoplegia, Chronic Progressive External / genetics*
  • Ophthalmoplegia, Chronic Progressive External / pathology
  • RNA, Transfer, Ile / genetics*

Substances

  • DNA, Mitochondrial
  • RNA, Transfer, Ile
  • Electron Transport Complex IV