A New Mitochondrial Transfer RNAPro Gene Mutation Associated With Myoclonic Epilepsy With Ragged-Red Fibers and Other Neurological Features

Arch Neurol. 2009 Mar;66(3):399-402. doi: 10.1001/archneurol.2008.576.

Abstract

Background: Pathogenic mutations of the human mitochondrial genome are associated with well-characterized, progressive neurological syndromes, with mutations in the transfer RNA genes being particularly prominent.

Objective: To describe a novel mitochondrial transfer RNA(Pro) gene mutation in a woman with a myoclonic epilepsy with ragged-red fibers-like disease. Design, Setting, and Patient Case report of a 49-year-old woman presenting with a myoclonic epilepsy with ragged-red fibers-like disease comprising myoclonic jerks, cerebellar ataxia, and proximal muscle weakness.

Results: Histochemical analysis of a muscle biopsy revealed numerous cytochrome-c oxidase-deficient, ragged-red fibers, while biochemical studies indicated decreased activity of respiratory chain complex I. Molecular investigation of mitochondrial DNA revealed a new heteroplasmic mutation in the TpsiC stem of the mitochondrial transfer RNA(Pro) gene that segregated with cytochrome-c oxidase deficiency in single muscle fibers.

Conclusions: Our case serves to illustrate the ever-evolving phenotypic spectrum of mitochondrial DNA disease and the importance of performing comprehensive mitochondrial genetic studies in the absence of common mitochondrial DNA mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochrome-c Oxidase Deficiency / complications
  • Cytochrome-c Oxidase Deficiency / genetics
  • DNA Mutational Analysis / methods
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex I / metabolism
  • Female
  • Humans
  • MERRF Syndrome / genetics*
  • MERRF Syndrome / pathology
  • Magnetic Resonance Imaging / methods
  • Middle Aged
  • Mutation*
  • RNA, Transfer, Pro / genetics*
  • Succinate Dehydrogenase / metabolism

Substances

  • DNA, Mitochondrial
  • RNA, Transfer, Pro
  • Succinate Dehydrogenase
  • Electron Transport Complex I