Leber's hereditary optic neuropathy is associated with the T14502C mutation in mitochondrial ND6 gene in three Han Chinese families

Objective To report the clinical,genetic,and molecular characterizations of three Chinese families with Leber's hereditary optic neuropathy (LHON).Methods Experimental study.Three Chinese Han families were identified with LHON.Ophthalmologic examinations were conducted on the probands and other matrilineal relatives of these families.Meanwhile,entire mitochondrial DNA (mtDNA) of three probands were amplified by PCR using 24 pairs of oligonucleotice primers with overlapping fragments.Results The probands had mild visual impairment.Strikingly,there was extremely low penetrance of visual impairment in these Chinese families,with a penetrance of 11.1％,10.0％ and 4.0％.Molecular analysis of mitochondrial DNA in these pedigrees revealed the absence of three common LHON associated with ND1 G3460A,ND4 G11778A,and ND6 T14484C mutations but there was a presence of homoplastic LHON associated with the ND6 T14502C (158V) mutation in probands and other matrilineal relatives.These mtDNA polymorphism sites belong to the Asian haplogroups M10a.The T14502C mutation in the ND6 gene,which is the substitution of a highly conserved isoleucine for valine (158V) at the amino acid position 58,had changed the structure and influenced the function of protein,causing visual impairment.Conclusion The results suggest that the ND6 T14502C mutation might be involved in the pathogenesis of Leber's hereditary optic neuropathy in the three Chinese Han families studied. Key words: Optic atrophy,hereditary,Leber;  Mutation;  DNA,Mitochondria;  Mitochondria Haplogroup ;  Penetrance