Tissue specific distribution of the 3243A->G mtDNA mutation

J Med Genet. 2006 Aug;43(8):671-7. doi: 10.1136/jmg.2005.039339. Epub 2006 Feb 20.


Background: The 3243A-->G is a common pathogenic mitochondrial DNA (mtDNA) point mutation causing a variety of different phenotypes. Segregation of this mutation to different tissues during embryonic life and postnatally is still enigmatic.

Objective: To investigate the tissue distribution of this mutation.

Methods: In 65 individuals from nine families segregating the 3243A-->G mutation, the mutation load (% mutated mtDNA) was determined in various tissues. Mutation load was measured in two to four cell types--blood leucocytes, buccal cells, skeletal muscle cells, and urine epithelial cells (UEC)--derived from all three embryogenic germ layers.

Results: There was a significant correlation among mutation loads in the four tissues (r = 0.80-0.89, p<0.0001). With blood serving as reference, the mutation load was increased by 16% in buccal mucosa, by 31% in UEC, and by 37% in muscle. There were significant differences between the mitotic tissues blood, buccal mucosa, and UEC (p<0.0001), but no difference between UEC and muscle. Using the present data as a cross sectional investigation, a negative correlation of age with the mutation load was found in blood, while the mutation load in muscle did not change with time; 75% of the children presented with higher mutation loads than their mothers in mitotic tissues but not in the post-mitotic muscle.

Conclusions: There appears to be a uniform distribution of mutant mtDNA throughout the three germ layers in embryogenesis. The significant differences between mutation loads of the individual tissue types indicate tissue specific segregation of the 3243A-->G mtDNA later in embryogenesis.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood / metabolism*
  • Child
  • DNA, Mitochondrial / genetics*
  • Epithelial Cells / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism*
  • Muscle, Skeletal / metabolism*
  • Mutation / genetics*
  • Organ Specificity


  • DNA, Mitochondrial