Molecular Bases of Leber’s Hereditary Optic Neuropathy in Chinese Population

Abstract

Purpose:: To understand the molecular mechanism of Leber’s hereditary optic neuropathy (LHON) in Chinese population.

Methods:: A large cohort of Han Chinese subjects with LHON were studied by clinical and genetic evaluation as well as molecular and biochemical analysis of mitochondrial (mt)DNA.

Results:: We have identified 297 Han Chinese LHON pedigrees with the variable penetrance and expressivity. Of these, 120 pedigrees carried ND4 G11778A mutation, 13 pedigrees harbored ND6 T14484C mutation, 5 pedigrees had the ND1 G3460A mutation, and 9 pedigrees carried the ND4 G11686A mutation, while other pedigrees lacked those mutations. Subsequently, we have conducted clinical and genetic evaluations and sequence analysis of complete mtDNA genome of 40 Chinese pedigrees. These mtDNA genomes belong to different haplogroups including D,C,B,H,F and M. Interestingly, the mt tRNAMet A4435G, the tRNAThr A15951G and tRNACys G5821A variants were implicated to influence the phenotypic expression of the primary ND4 G11778A mutation in Chinese families.

Conclusions:: These data revealed the spectrum and frequency of mtDNA mutations associated with LHON in Chinese population. Our data provided the first direct genetic and biochemical evidences that mitochondrial variants modulate the phenotypic expression of vision loss associated with these primary mtDNA mutations.

Keywords: optic nerve • mitochondria • genetics