<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

Abstract
Figure/Table
References (0)
Related Citation (15)

Download: PDF (1577 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

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

Received: 16 September 2019

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	XU Man
	CI Xiaorui
	LYU Yuanyuan
	ZHANG Juanjuan
	GUAN Minxin

URL:

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

[1] 仲俊维, 陈鼎, 余新平, 等. Leber遗传性视神经萎缩病外显率的影响因素研究进展[J]. 国际眼科杂志, 2015, 15(11): 1888-1891.
[2] YU-WAI-MAN P, GRIFFITHS P G, CHINNERY P F. Mitochondrial optic neuropathies-disease mechanisms and therapeutic strategies[J]. Prog Retin Eye Res, 2011, 30(2): 81- 114.
[3] WALLACE D C, SINGH G, LOTT M T, et al. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy[J]. Science, 1988, 242(4884): 1427-1430.
[4] NEUHANN T, RAUTENSTRAUSS B. Genetic and phenotypic variability of optic neuropathies[J]. Expert Rev, 2013, 13(4): 357-367.
[5] BROWN M D, TORRONI A, RECKORD C L, et al. Phylogenetic analysis of Leber’s hereditary optic neuropathy mitochondrial DNA’s indicates multiple independent occurrences of the common mutations[J]. Hum Mutat, 1995, 6(4): 311-325.
[6] MACKEY D A, OOSTRA R J, ROSENBERG T, et al. Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy[J]. Am J Hum Genet, 1996, 59(2): 481-485.
[7] MASHIMA Y, YAMADA K, WAKAKURA M, et al. Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber’s hereditary optic neuropathy[J]. Curr Eye Res, 1998, 17(4): 403-408.
[8] QU J, LI R H, ZHOU X T, et al. The novel A4435G mutation in the mitochondrial tRNAMet may modulate the phenotypic expression of the LHON-associated ND4 G11778A mutation in a Chinese family. 2005年浙江省眼科学术会议论文集[C]. 杭州: 浙江省眼科学术分会, 2005: 119-120.
[9] 张永梅, 冀延春, 刘晓玲, 等. 线粒体tRNAGlu A14693G可能是与Leber遗传性视神经病变相关的基因突变[J]. 遗传, 2010, 32(4): 353-359.
[10] LI R H, QU J, ZHOU X T, et al. The mitochondrial tRNAThr A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 G11778A mutation in a Chinese family[J]. Gene, 2006, 376(1): 79-86.
[11] ZHANG J J, JI Y C, LIU X L, et al. Leber's hereditary optic neuropathy caused by a mutation in mitochondrial tRNAThr in eight Chinese pedigrees[J]. Mitochondrion, 2017, 42: 84- 91.
[12] ZHANG A M, JIA X Y, ZHANG W, et al. Is mitochondrial tRNAphe variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A?[J]. PLoS One, 2011, 6(10): e26511.
[13] BANDELT H J, KLOSS-BRANDSTATTER A, RICHARDS M B, et al. The case for the continuing use of the revised Cambridge Reference Sequence (rCRS) and the standardization of notation in human mitochondrial DNA studies[J]. J Hum Genet, 2014, 59(2): 66-77.
[14] WALLACE D C, FAN W. Energetics, epigenetics, mitochondrial genetics[J]. Mitochondrion, 2010, 10(1): 12-31.
[15] VAN OVEN M, KAYSER M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation [J]. Hum Mutat, 2009, 30(2): E386-E394.
[16] LU Z J, GLOOR J W, MATHEWS D H. Improved RNA secondary structure prediction by maximizing expected pair accuracy[J]. RNA, 2009, 15(10): 1805-1813.
[17] LI P T, VIEREGG J, TINOCO I Jr. How RNA unfolds and refolds[J]. Annu Rev Biochem, 2008, 77: 77-100.
[18] LIANG M, GUAN M Q, ZHAO F X, et al. Leber’s hereditary optic neuropathy is associated with mitochondrial ND1 T3394C mutation[J]. Biochem Biophys Res Commun, 2009, 383(3): 286-292.
[19] 孙艳红, 韦企平, 周剑, 等. 中国Leber遗传性视神经病变 14484 位点突变的家系分析[J]. 国际眼科杂志, 2004, 4(3): 460-462.
[20] QU J, LI R H, TONG Y, et al. Only male matrilineal relatives with Leber’s hereditary optic neuropathy in a large Chinese family carrying the mitochondrial DNA G11778A mutation[J]. Biochem Biophys Res Commun, 2005, 328(4): 1139-1145.
[21] QU J, ZHOU X T, ZHANG J J, et al. Extremely low penetrance of Leber’s hereditary optic neuropathy in 8 Han Chinese families carrying the ND4 G11778A mutation[J]. Ophthalmology, 2009, 116(3): 558-564.
[22] 孟祥娟, 朱金萍, 高敏, 等. 中国人群携带m.14484T>C突变的Leber’s遗传性视神经病变线粒体单体型及多态位点分析[J]. 遗传, 2014, 36(4): 336-345.
[23] CHEN X W, NIE Z P, WANG F, et al. Late onset nonsyndromic hearing loss in a Dongxiang Chinese family is associated with the 593T>C variant in the mitochondrial tRNAPhe gene[J]. Mitochondrion, 2017, 35: 111-118.