Tong Yi, Mao Yijian, Zhou Xiangtian, Yang Li, Zhang Juanjuan, Cai Wanshi, Zhao Fuxing, Wang Xinjian, Lu Fan, Qu Jia, Guan Min-Xin
School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China.
Biochem Biophys Res Commun. 2007 Jun 1;357(2):524-30. doi: 10.1016/j.bbrc.2007.03.189. Epub 2007 Apr 9.
We report here the clinical, genetic, and molecular characterization of one Han Chinese family with maternally transmitted Leber's hereditary optic neuropathy (LHON). Three of seven matrilineal relatives in this family exhibited the variable degree of central vision loss at the age of 12, 14, and 16 years old, respectively. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the ND1 G3460A mutation and 47 other variants, belonging to the Asian haplogroup M7b2. The G3460A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the homoplasmic A14693G mutation is of special interest as it was implicated to be associated with other mitochondrial disorders. This mutation is located at the TpsiC-loop, at conventional position 54 of tRNA(Glu). The uridine at this position (U54), which is highly conserved from bacteria to human mitochondria, has been implicated to be important for tRNA structure and function. Thus, the A14693G mutation may alter the tertiary structure of this tRNA, cause a failure in this tRNA metabolism, thereby worsening the mitochondrial dysfunction associated with the primary G3460A mutation. Therefore, the tRNA(Glu) A14693G mutation may have a potential modifier role in the phenotypic manifestation of the primary LHON-associated G3460A mutation in this Chinese family.
我们在此报告一个母系遗传的Leber遗传性视神经病变（LHON）的汉族家庭的临床、遗传和分子特征。该家族中七名母系亲属中的三名分别在12岁、14岁和16岁时出现了不同程度的中心视力丧失。对这个家系的完整线粒体DNA进行序列分析，发现存在ND1 G3460A突变和其他47个变异，属于亚洲单倍群M7b2。G3460A突变在这个中国家庭的母系亲属中呈纯合状态存在。在其他变异中，纯合的A14693G突变特别值得关注，因为它被认为与其他线粒体疾病有关。该突变位于tRNA（Glu）的TpsiC环，在常规位置54处。这个位置的尿苷（U54）从细菌到人类线粒体都高度保守，被认为对tRNA的结构和功能很重要。因此，A14693G突变可能会改变该tRNA的三级结构，导致该tRNA代谢失败，从而加重与原发性G3460A突变相关的线粒体功能障碍。因此，tRNA（Glu）A14693G突变可能在这个中国家庭中对原发性LHON相关G3460A突变的表型表现具有潜在的修饰作用。
