摘要目的:对13个携带线粒体tRNA Thr 15924A>G突变Leber遗传性视神经病变(Leber’s hereditary optic neuropathy，LHON)家系进行的线粒体遗传学和功能分析。 方法:对收集的13个携带m.15924A>G突变家系进行眼科学检查、线粒体全基因组测序、线粒体单体型分析，对照组和突变组细胞进行活性氧和线粒体膜电位分析。结果:患者的临床表现及眼科检查均符合LHON的典型特征，平均发病年龄为14.387岁，13个家系平均外显率为14.02%。患者线粒体单体亚型分别为M10、D、C、B、F，分布集中在M、N单体型，其中M单体型占比69.2%，N单体型占30.8%，且携带m.15924A>G突变LHON患者单体型以M、N为主，单体型M发生视力损伤的风险比单体型N大( P＝0.027)。m.15924A>G突变破坏了31T-39A碱基对，影响tRNA Thr反密码子臂结构的稳定性，自由能改变。细胞实验结果证明突变组细胞活性氧水平增加( P＝0.019)，线粒体膜电位水平降低( P<0.001)。 结论:m.15924A>G突变破坏了tRNA Thr 31T-39A碱基对，自由能改变，细胞活性氧增加，膜电位降低，表明该突变影响tRNA Thr结构的稳定性，导致线粒体功能障碍。

abstractsObjective:To analyze the mitochondrial haplotype of 13 families carrying mitochondrial tRNA Thr15924A>G mutation of Leber hereditary optic neuropathy(Leber’s hereditary optic neuropathy, LHON). Methods:13 m. 15924A>G mutant families were examined by ophthalmology, mitochondrial genome sequencing and mitochondrial haplotype analysis.Results:The clinical manifestations and ophthalmological examination of the patients were consistent with the typical characteristics of LHON. The mean age of onset was 14.387 years old, and the mean penetrance of the 13 families was 14.02%.The mitochondrial monomer subtypes of the patients were M10, D, C, B, and F, and the distribution was concentrated in M and N haplotypes, among which M haplotypes accounted for 69.2% and N haplotypes accounted for 30.8%. In LHON patients with m. 15924A>G mutation, the haplotypes were mainly M and N, and the risk of visual impairment of haplotype M was greater than that of haplotype N ( P=0.027).m.15924A>G mutation destroyed 31T-39A base pair, affected the stability of tRNA Thr anti-codon arm structure, and changed the free energy.The results of cell experiment showed that reactive oxygen species increased ( P=0.019) and mitochondrial membrane potential decreased ( P<0.001) in mutant group. Conclusion:The mutation of m. 15924A>G destroys the tRNA Thr31T-39A base pair, changes the free energy, increases the reactive oxygen species, and decreases the membrane potential, indicating that the mutation affects the stability of tRNA Thr structure and leads to mitochondrial dysfunction.