The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS

Ann Neurol. 1999 Dec;46(6):916-9. doi: 10.1002/1531-8249(199912)46:6<916::aid-ana16>;2-r.


We report on 4 male patients with clinical, radiological, and muscle biopsy findings typical of the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) phenotype. Skeletal muscle mitochondrial DNA (mtDNA) analysis showed that all patients harbored a heteroplasmic G13513A mutation in the ND5 subunit gene. One of these cases (Patient 1) presented with symptoms characteristic of Leber's hereditary optic neuropathy (LHON) 2 years before the first stroke-like episode. Quantitative analysis in several postmortem tissue sections showed that the relative proportions of mutant mtDNA were generally lower than those reported with other pathogenic mtDNA mutations. Single-fiber polymerase chain reaction studies demonstrated significantly higher amounts of mutant mtDNA in ragged red fibers (RRFs) compared with non-RRFs. This study indicates that the G13513A transition is likely to be pathogenic, that it can cause an LHON/MELAS overlap syndrome, and that it may be a more frequent cause of MELAS than previously recognized.

Publication types

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

MeSH terms

  • Adult
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex I
  • Electron Transport Complex IV / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • MELAS Syndrome / genetics*
  • Male
  • Mitochondria, Muscle / genetics
  • Mitochondria, Muscle / pathology
  • Muscle, Skeletal / pathology
  • NADH, NADPH Oxidoreductases / genetics
  • Optic Atrophies, Hereditary / genetics*
  • Point Mutation*
  • Polymerase Chain Reaction


  • DNA, Mitochondrial
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex IV
  • Electron Transport Complex I