Abstract

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.