Analysis of Three Primary mtDNA Mutations in 155 Patients with Leber’s Hereditary Optic Neuropathy

Background: Leber’s Hereditary Optic Neuropathy (LHON) is a maternal inherited disease caused by mitochondrial DNA (mtDNA) mutations. The aim of the current study is to analysis the frequencies of mitochondrial ND1 G3460A, ND4 G11778A and ND6 T14484C mutations in patients with LHON. Methods: : Our study enrolled 155 patients with LHON and 83 controls, PCR-Sanger sequencing was performed to screen the presence of these primary mutations. Moreover, we performed clinical, genetic and molecular characterizations of five Chinese families carrying LHON-related three primary mutations. Results: : 28 patients with G3460A (18.1%), 86 patients with G11778A (55.5%) and 32 patients carrying T14484C mutation (20.6%) were identified. However, none of these primary mutations were identified in controls. Among them, one patient carrying G3460A, two patients with G11778A and two patients with T14484C mutation had an obvious family history of LHON. Clinical evaluation of these pedigrees showed the variable clinical phenotypes with different age at onset of LHON. Sequence analysis of the complete mtDNA genes from the matrilineal relatives suggested the presence of these primary mutations. However, the lack of any functional variants in mtDNA genes revealed that mitochondrial haplogroups or haplotypes may not play important roles in the clinical phenotypic manifestation of LHON-associated primary mutations. Conclusions: : Our data indicated that screening for the mtDNA primary mutations was necessary for early detection, prevention and diagnosis of LHON.