Sequence analysis of the complete mitochondrial genome in patients with mitochondrial encephaloneuromyopathies lacking the common pathogenic DNA mutations

Biochem Biophys Res Commun. 2004 Nov 5;324(1):360-4. doi: 10.1016/j.bbrc.2004.09.058.


The purpose of this study was to identify novel mitochondrial deoxyribonucleic acid (mtDNA) mutations in a series of patients with clinical and/or morphological features of mitochondrial dysfunction, but still no genetic diagnosis. A heterogeneous group of clinical disorders is caused by mutations in mtDNA that damage respiratory chain function of cell energy production. We developed a method to systematically screen the entire mitochondrial genome. The sequence-data were obtained with a rapid automated system. In the six mitochondrial genomes analysed we found 20 variants of the revised Cambridge reference sequence [Nat. Genet. 23 (1999) 147]. In skeletal muscle nineteen novel mtDNA variants were homoplasmic, suggesting secondary pathogenicity or co-responsibility in determination of the disease. In one patient we identified a novel heteroplasmic mtDNA mutation which presumably has a pathogenic role. This screening is therefore useful to extend the mtDNA polymorphism database and should facilitate definition of disease-related mutations in human mtDNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • DNA, Mitochondrial / analysis*
  • Evolution, Molecular
  • Female
  • Genome
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / genetics*
  • Mitochondrial Encephalomyopathies / genetics*
  • Mitochondrial Encephalomyopathies / physiopathology
  • Mutation*
  • Polymorphism, Genetic
  • Sequence Analysis, DNA*


  • DNA, Mitochondrial