<div>线粒体tRNAPhe 593T>C对m.14484T>C相关 Leber遗传性视神经病变表型表达的影响</div>

doi:10.3969/j.issn.2095-9400.2020.05.002

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摘要目的：探讨线粒体tRNAPhe 593T＞C对 MT ND6 14484T＞C相关Leber遗传性视神经病变（LHON）发生发展中的作用。方法：对收集的742例汉族LHON患者和376例对照进行线粒体全基因组测序，并对其中4个LHON家系进行临床、遗传和分子生物学特征评估。结果：4个LHON家系（WZ133、WZ1224、WZ1225和 WZ1260）的外显率分别为42.9%、12.5%、12.5%和5.6%，发病年龄9～23岁，平均发病年龄为16岁。线粒体全基因组分析显示WZ133携带m.14484T＞C和m.593T＞C突变，而其他3个家系仅携带m.593T＞C突变。线粒体tRNA二级结构分析发现：m.593T＞C突变的tRNAPhe二级结构发生改变，且自由能增加，使得tRNAPhe结构的稳定性降低，从而导致线粒体功能紊乱。结论：tRNAPhe 593T＞C可能对m.14484T＞C相关LHOH的表型表达有影响。

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关键词 ： Leber遗传性视神经病变, 线粒体tRNAPhe, 突变, 外显率, 中国人群

Abstract：Objective: To investigate the role of mitochondrial tRNAPhe 593T>C in the development of Leber’s hereditary optic neuropathy (LHON)-associated with the MT-ND6 14484T>C mutation. Methods: A cohort of 742 Han Chinese subjects with LHON and 376 control subjects underwent sequence analysis of the complete mitochondrial DNA. 4 Chinese families with LHON were evaluated for clinical, genetic and molecular biological characteristics. Results: The penetrance of vision loss in these pedigrees (WZ133, WZ1224, WZ1225 and WZ1260) was 42.9%, 12.5%, 12.5% and 5.6%, respectively. The age-at-onset of vision impairment in the four families varied from 9 to 23 years. The average age-of-onset was 16. Sequence analysis of mitochondrial genome indicated that WZ133 carried m.14484T>C and m.593T>C, while the other three families only carried m.593T>C. Analysis of the secondary structure of mitochondrial tRNA showed that this mutation resulted in a secondary structure change and higher free energy of tRNAPhe. The alterations reduced the stability of tRNAPhe structure and led to mitochondrial dysfunction. Conclusion: The tRNAPhe 593T>C mutation may have a potential modifier role in the phenotypic manifestation of the primary LHON-associated m.14484T>C mutation.

Key words： Leber’s hereditary optic neuropathy mitochondrial tRNAPhe mutation penetrance the Chinese people

收稿日期: 2019-09-16

基金资助:国家自然科学基金资助项目（81200724）；浙江省医药卫生科技计划项目（2019RC219）；温州市基础性科研项目（Y20190067）；温州医科大学附属眼视光医院院内创新引导课题（YNCX3201901）；浙江省自然科学基金资助项目（LY20C060003）。

通讯作者: 管敏鑫，教授，Email：gminxin88@zju.edu.cn。

作者简介: 徐曼（1994-），女，陕西商洛人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 10.3969/j.issn.2095-9400.2020.05.002 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I5/356

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