Objectives: To determine the incidence and clinical significance of peripheral blood heteroplasmy and the presence of normal and mutant mitochondrial DNA in Leber's hereditary optic neuropathy through evaluation of a large series of families with the 11778 mutation and to evaluate the pattern of transmission of heteroplasmy.
Design: We studied heteroplasmy in 75 visually symptomatic patients with the 11778 mutation and in 101 asymptomatic family members. We compared the incidence of heteroplasmy in these two groups, collected clinical information for each symptomatic patient, and calculated the incidence of heteroplasmy within each generation of the pedigrees.
Results: We detected heteroplasmy in 24 (14%) of the 176 persons tested. Kaplan-Meier life-table analysis suggests that heteroplasmic persons are more likely to remain asymptomatic than those who are homoplasmic mutant (males, P = .17; females, P = .14). However, heteroplasmic persons who become symptomatic do not seem to differ clinically from symptomatic patients who are homoplasmic mutant. Pedigree analysis reveals a strong tendency for progression from heteroplasmy toward homoplasmy in subsequent generations (P = .001).
Conclusion: Heteroplasmy for the 11778 mutation seems to play a role in the clinical expression of Leber's hereditary optic neuropathy and tends to progress toward homoplasmy in successive generations.