Segregation of the ND4/11778 and the ND1/3460 mutations in four heteroplasmic LHON families.

Leber hereditary optic neuropathy (LHON) is an ocular disease associated with mutations in the mitochondrial DNA (mtDNA). The level of heteroplasmy in the mtDNA mutations ND4/11778 and ND1/3460 was followed over a period of 4–12 years in blood samples taken from nine members of four heteroplasmic LHON families. In addition, hair follicle and urinary tract epithelium samples of one individual were studied. The quantification of heteroplasmy was performed using the solid-phase minisequencing method. Only minor and random shifts in the heteroplasmy levels were observed over time, but there were no systematic changes towards an increasing or decreasing proportion of either LHON mutant in the individuals. This indicates that there is no selection for either mtDNA genotype but the segregation of the wild-type mtDNAs and those carrying LHON mutations is a stochastic process governed by random genetic drift. In this respect, LHON mutations seem to behave like neutral polymorphisms.