Heteroplasmy of Leber hereditary optic neuropathy and clinical expression in Chinese pedigrees with 11778A mutation

To investigate the proportion of 11778A mutation in Chinese individuals with Leber hereditary optic neuropathy (LHON), analyze its relationship with prevalence (penetrance) and the severity of visual loss. Methods Seven Chinese pedigrees of LHON with 11778A mutation were investigated and clinically evaluated. Peripheral blood was drawn from 96 maternal relatives and the proportion of mutant 11778A was measured by fluorescence-based primer extension and restriction fragment length polymorphism analysis. The relationships between the proportion of mutant 11778A with prevalence and severity of visual acuity were compared. Results One hundred maternal relatives (46 male, 54 female) were contained in the 7 pedigrees and 22 male, 15 female were affected. The visual loss can be great difference for members from different pedigrees but may be similar in the same pedigree. In 4 pedigrees, the proportion of mutant 11778A was 100% (homoplasmy) in each of the 55 members. In other 3 pedigrees, which included 41 individuals and 16 of them had symptom and 25 without symptom, except one without symptom had normal genotype, the proportion of mutant 11778A was 27% to 92% (mean 75.1%) in symptomatic members and 12% to 96% (mean 69.1%) in asymptomatic individuals (heteroplasmy). There was no statistical difference between the proportion of mutant mtDNA in these two groups (P = 0.31, T test). And there was no relationship between the proportion of mutant mtDNA with the severity of visual loss. Conclusions Most individuals who possess similar proportion of 11778A mutation have different prevalence of LHON and severity of visual loss. The proportion of mutant 11778A itself cannot explain the variation in the clinical phenotype of LHON. [Wen-cui Wan, Yu Zhu, Xue-min Jin. Heteroplasmy of Leber hereditary optic neuropathy and clinical expression in Chinese pedigrees with 11778A mutation Life Sci J;9(4):2760-2763]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 406