Intragenic inversion of mtDNA: a new type of pathogenic mutation in a patient with mitochondrial myopathy

Am J Hum Genet. 2000 Jun;66(6):1900-4. doi: 10.1086/302927. Epub 2000 Apr 17.


We report an unusual molecular defect in the mitochondrially encoded ND1 subunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitochondrial myopathy and isolated complex I deficiency. The mutation is an inversion of seven nucleotides within the ND1 gene, which maintains the reading frame. The inversion, which alters three highly conserved amino acids in the polypeptide, was heteroplasmic in the patient's muscle but was not detectable in blood. This is the first report of a pathogenic inversion mutation in human mtDNA.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Inversion*
  • Conserved Sequence / genetics
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex I
  • Humans
  • Male
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / pathology
  • Mitochondrial Myopathies / enzymology
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / pathology
  • Mitochondrial Myopathies / physiopathology
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation / genetics*
  • NADH, NADPH Oxidoreductases / deficiency
  • NADH, NADPH Oxidoreductases / genetics*
  • Polymorphism, Restriction Fragment Length
  • Protein Subunits
  • Recombination, Genetic / genetics


  • DNA, Mitochondrial
  • Protein Subunits
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I