Objective To observe the molecular genetic characteristics of seven Chinese families with Leberprime;s hereditary optic neuropathy (LHON). Methods Ophthalmologic examinations were performed on seven probands, maternal members from seven Chinese families and 134 healthy controls. There were two LHON patients in seven Chinese families except probands. The entire mitochondrial genome was amplified using 24 pairs of oligonucleotide primers with overlapping fragments.The mutational site was analyzed through comparison of the Results and Cambridge reference sequence. The penetrance of mutation site was calculated and the haplotype was analyzed. Results Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated with ND4 G11778A, ND1 G3460A and ND6 T14484C mutations. The ND1 T3394C mutation in probands and other matrilineal relatives was present in four out of 134 Chinese healthy controls. Strikingly, these families exhibited very low penetrance of visual impairment. The penetrance was 12.50%, 22.22%, 16.76%, 6.25%, 9.09%, 11.11% and 28.57%. The Results of phylogenetic tree analysis of submitochondrial haplotype showed that these mtDNA polymorphism sites belong to the Asian haplogroups M9, M9, M, D4, M, M9 and M9. Conclusions T3394C mutation exists in seven Chinese LHON pedigrees, and the penetrance was ranged from 6.25% to 28.57%. The patients have different clinical manifestations.
Objective To find the new mutations of Leber's hereditary optic neuropathy (LHON). Methods Two LHON families were enrolled in this study. The probands and all maternal members in this two families were underwent ophthalmologic examinations. The ages of probands were seven and 14 years old respectively. A total of 358 healthy adults were enrolled in this study as control group. The genomic DNA from whole blood of participants were extracted. The entire mitochondrial genome of probands were PCR amplified and sequenced in 24 overlapping fragments using primers as designed. At the same time, the mtDNA of maternal relatives and 358 controls were also detected. Fourteen primate species were selected from GenBank to analyzed the phylogenetics of mitochondrial sequence. Results There was no ND4 G11778A, ND1 G3460A, ND6 T14484C mutational site in all maternal members. Molecular analysis of mtDNA in this two families identified the homoplasmic tRNAGluA14683G mutation and distinct set of variants belonging to the Asian haplogroup F1a1 and G2. The site was at theTpsi;C stem oftRNAGlu and extremely conserved among 14 primate species. It was anticipated that the A14683G increased the highly conserved C-G basepairing. Furthermore, the A14683G was absence in control group. Conclusion The tRNAGluA14683G mutation is likely a new mutation associated with LHON.