Techniques and pitfalls in the detection of pathogenic mitochondrial DNA mutations

J Mol Diagn. 2003 Nov;5(4):197-208. doi: 10.1016/S1525-1578(10)60474-6.


Mutations in the mitochondrial DNA (mtDNA) are now recognized as major contributors to human pathologies and possibly to normal aging. A large number of rearrangements and point mutations in protein coding and tRNA genes have been identified in patients with mitochondrial disorders. In this review, we discuss genotype-phenotype correlations in mitochondrial diseases and common techniques used to identify pathogenic mtDNA mutations in human tissues. Although most of these approaches employ standard molecular biology tools, the co-existence of wild-type and mutated mtDNA (mtDNA heteroplasmy) in diseased tissues complicates both the detection and accurate determination of the size of the mutated fractions. To address these problems, novel approaches were developed and are discussed in this review.

Publication types

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

MeSH terms

  • DNA Mutational Analysis / methods*
  • DNA, Mitochondrial / genetics*
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / pathology
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Mutation / genetics*


  • DNA, Mitochondrial