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

doi:10.3724/SP.J.1005.2014.0336

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HEREDITAS ›› 2014, Vol. 36 ›› Issue (4): 336-345.doi: 10.3724/SP.J.1005.2014.0336

The analysis of mitochondrial DNA haplogroups and variants for Leber’s hereditary optic neuropathy in Chinese families carrying the m.14484T>C mutation

Xiangjuan Meng^1,2, Jinping Zhu^1,2, Min Gao^1,2, Sai Zhang^1,2, Fuxin Zhao², Juanjuan Zhang⁵, Xiaoling Liu², Qiping Wei³, Yi Tong², Minglian Zhang⁴, Jia Qu², Minxin Guan^1,5

1. Zhejiang Provincial Key Laboratory of Medical Genetics, Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou 325035, China;
2. School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, China;
3. Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078, China;
4. Xingtai Eye Hospital, Hebei Province, Xingtai 054001, China;
5. Institute of Genetics, Zhejiang University, Hangzhou 310023, China

Received:2013-09-23 Revised:2013-10-28 Online:2014-04-20 Published:2014-03-20

Abstract

Abstract:

The m.14484T>C mutation in mitochondrial ND6 gene (MT-ND6) is a primary mutation underlying the development of Leber’s hereditary optic neuropathy (LHON) , but by itself not enough to cause visual loss. To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T>C mutation, we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON. A total of 67 affected subjects carried the homoplasmic m.14484T>C mutation, accounting for 5.7% of this LHON population. The penetrances of optic neuropathy among 51 pedigrees carrying the m.14484T>C mutation ranged from 5.6% to 100.0%, with the average of 21.5%. The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups. The frequencies of haplogroup A and haplogroup F were sig-nificantly less in the LHON mtDNA samples than those in 106 Chinese controls. On the other hand, the haplogroup M10a accounted for 9.8% of the patient’s mtDNA samples but was absent in 106 Chinese controls. Strikingly, the average pene-trance (46.13%) of optic neuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those car-rying other mtDNA haplogroups. These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss.

Key words: Leber’s hereditary optic neuropathy(LHON), mitochondrial, mutation, haplogroup, penetrance

Xiangjuan Meng, Jinping Zhu, Min Gao, Sai Zhang, Fuxin Zhao, Juanjuan Zhang, Xiaoling Liu, Qiping Wei, Yi Tong, Minglian Zhang, Jia Qu, Minxin Guan. The analysis of mitochondrial DNA haplogroups and variants for Leber’s hereditary optic neuropathy in Chinese families carrying the m.14484T>C mutation[J]. HEREDITAS, 2014, 36(4): 336-345.

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The analysis of mitochondrial DNA haplogroups and variants for Leber’s hereditary optic neuropathy in Chinese families carrying the m.14484T>C mutation

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