线粒体tRNATyrA5834G突变与Leber遗传性视神经病变的相关性

doi:10.3969/j.issn.2095-9400.2020.09.001

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摘要目的：探讨线粒体tRNATyrA5834G突变与Leber遗传性视神经病变（LHON）的相关性。方法：对2个携带tRNATyrA5834G突变的LHON家系进行临床和分子遗传学特征等分析评估，对家系先证者和其他成员进行详细的眼科相关检查、线粒体全基因组分析、种系发生学分析及单体型分析。结果：先证者的临床症状及眼科相关检查均符合典型LHON表现，家系其他成员无异常。2个家系均未携带ND1 G3460A和ND4 G11778A及ND6 T14484C这3个原发突变位点，多态性变异位点均属于东亚单体型M7b。2个先证者均携带具有高度保守性的A5834G和T12811C突变位点，其中A5834G在17个物种中的保守系数为87.5%。结论：线粒体tRNATyrA5834G突变可能是与LHON相关的mtDNA突变位点，同时低外显率提示其他因素，如核修饰基因、环境等可能影响这2个家系的表型表达。

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	胡翠芳
	孔万仲
	陈孟权
	梁敏
	管敏鑫

关键词 ： Leber遗传性视神经病变, 外显率, 线粒体DNA, 线粒体突变, 眼底检查

Abstract：Objective: To investigate the possible relationship between mitochondrial tRNATyrA5834G mutation and Leber’s hereditary optic neuropathy (LHON). Methods: Clinical data were collected from two pedigrees, and detailed ophthalmological examination and mitochondrial genomes were conducted for the two proband members.Detailed eye examinations mitochondrial whole genome analysis phylogenetic analysis and haplotype analysis were performed on probands and other members of the pedigrees. Results: The clinical symptoms and ophthalmological examinations of the probands were in line with typical LHON manifestations,
and other members of the family were not abnormal. The two pedigrees did not carry the three primary mitochondrial mutation sites of ND1 G3460A and ND4 G11778A and ND6 T14484C. The polymorphic mutation sites belonged to the East Asian haplotype M7b. Both probands carried highly conserved A5834G mutation sitesamong which the conservative coefficient of A5834G in 17 species was 87.5%. Conclusion: The mitochondrial tRNATyrA5834G mutation may be the mtDNA mutation site associated with LHON and the low penetrance rate suggests that other factors (including nuclear modified genes environment etc.) may affect the phenotypicexpression of these two families.

Key words： Leber’s hereditary optic neuropathy penetrance mitochondrial DNA mitochondrial mutation fundus examination

收稿日期: 2020-04-26

基金资助:国家自然科学基金青年基金资助项目（81600769）。

通讯作者: 管敏鑫，教授，博士生导师，Email：gminxin88@gmail.com。

作者简介: 胡翠芳（1991-），女，福建泉州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 10.3969/j.issn.2095-9400.2020.09.001 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I9/689

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