High penetrance of sequencing errors and interpretative shortcomings in mtDNA sequence analysis of LHON patients

Biochem Biophys Res Commun. 2007 Jan 12;352(2):283-91. doi: 10.1016/j.bbrc.2006.10.131. Epub 2006 Nov 3.


For identifying mutation(s) that are potentially pathogenic it is essential to determine the entire mitochondrial DNA (mtDNA) sequences from patients suffering from a particular mitochondrial disease, such as Leber hereditary optic neuropathy (LHON). However, such sequencing efforts can, in the worst case, be riddled with errors by imposing phantom mutations or misreporting variant nucleotides, and moreover, by inadvertently regarding some mutations as novel and pathogenic, which are actually known to define minor haplogroups. Under such circumstances it remains unclear whether the disease-associated mutations would have been determined adequately. Here, we re-analyse four problematic LHON studies and propose guidelines by which some of the pitfalls could be avoided.

Publication types

  • Evaluation Study
  • Meta-Analysis

MeSH terms

  • Artifacts
  • DNA Mutational Analysis / methods
  • DNA, Mitochondrial / genetics*
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing / methods*
  • Genetic Variation / genetics
  • Humans
  • Mutation
  • Optic Atrophy, Hereditary, Leber / diagnosis*
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Penetrance
  • Quality Assurance, Health Care / methods*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*


  • DNA, Mitochondrial