Intergenerational transmission of pathogenic heteroplasmic mitochondrial DNA

Abstract

Purpose: To study the pattern of intergenerational transmission of pathogenic mitochondrial DNA with heteroplasmic A3243G, G8363A, A8344G, T8993G, and T8993C mutations. Methods: The mutant load in the carrier mother and her offspring was measured in a total of 79 transmissions. Statistical analysis was performed to determine whether the intergenerational change in heteroplasmic mutant mtDNA is significant. Results: Our results demonstrate that A3243G and T8993G mutant mtDNAs are significantly increased in blood, hair follicles, and buccal mucosal cells, during intergenerational transmission, whereas the intergenerational increase in T8993C and A8363G mutant mtDNA is not significant. Unlike previous reports, in one large family with A8344G mutation, the mutant load was slightly increased, instead of decreased, during transmission. There is no significant difference in the intergeneration transmission of mutant mtDNA to male or female offspring. Conclusion: Intergenerational transmission of heteroplasmic A3243G and T8993G mtDNA results in significant increase of mutant mtDNA in the offspring. Transmission of T8993C, G8363A, and A8344G does not result in significant intergenerational change in mutant load. Tissue specificity and genetic background may play important roles in the transmission of pathogenic heteroplasmic mtDNA.