中文摘要：

Leber遗传性视神经病变变（Leber’s hereditary optic neuropathy，LHON）是一种与线粒体DNA（Mito-chondrialDNA，mtDNA）突变相关的母系遗传性眼科疾病。文章报道了两例具有典型LHON临床、分子遗传特征的中国汉族家系。首先通过对家系先证者和其他成员进行眼科相关检查，发现两个家系成员中视力都仅有先证者一人损害严重，即外显率很低。经常规的方法对母系成员进行mtDNA测序及相关软件分析，结果发现携带ND4G11696A和ND5T12338C同质性突变位点，多态性变异位点均属于东亚单体型F2。线粒体DNAND4G11696A是一个已知的与LHON相关的突变位点，而T12338C位于线粒体氧化磷酸化复合体Ⅰ亚基ND5的第2个碱基，该突变使起始密码子由蛋氨酸转变成苏氨酸，并且紧连tRNALeu（CUN）的3’末端。这可能影响tRNAkLeu（CUN）空间结构和稳定性发生改变，以及起始密码子改变导致线粒体ND5蛋白合成功能受损和ATP障碍，最终导致需求能量高的视神经受损和视力损害。因此，线粒体ND4G11696A和ND5T12338C突变可能协同作用Leber遗传性视神经病变的发生，是与LHON相关的mtDNA突变位点，但外显率很低说明突变本身不足以造成LHON的表型表达，提示其他修饰因子（核修饰基因、环境等）可能对这两个家系发病起协同作用。

英文摘要：

Leber＇s hereditary optic neuropathy （LHON） associated with mitochondrial DNA mutation is a maternally inherited eye disease. We reported here the clinical, genetic and molecular characterization of two Han Chinese families with Leber＇s hereditary optic neuropathy. Ophthalmologic examinations revealed that the variable severity and age-of-onset in visual impairment among probands and other matrilineal relatives of these families. Strikingly, there were extremely low penetrances of visual impairment in these families. Sequence analysis of complete mitochondrial genomes in these pedi- grees identified the homoplasmic ND4 G11696A and ND5 T12338C mutation and distinct sets of polymorphism belonging to haplogroups F2. It is well known that mitochondrial DNA ND4 G11696A is associated with LHON. The ND5 T12338C mutation resulted in replacement of the first amino acid, translation-initiating methionine with a threonine, and shortening two amino acids of ND5. This mutation also locates in two nucleotides adjacent to the 3＇ end of the tRNAt~ctrN）. Thus, this mutation may alter structural formation and stabilization of functional tRNA, thereby leading to a failure in protein synthe- sis and mitochondrial dysfunction involved in visual impairment. Therefore, the ND4 G11696A and ND5 T12338C muta- tion is likely associated with LHON in these two Chinese families. But these families exhibited extremely low penetrances of visual impairment. It suggests that other factors, such as nuclear modifier gene（s） or environmental factor（s）, may play a role in the phenotypic expression of the LHON-associated ND4 G 11696A and ND5 T 12338C mutation.