Lyu Yuanyuan, Xu Man, Chen Jie, Ji YanChun, Guan Min-Xin, Zhang Juanjuan
School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China.
School of Laboratory Medicine and Life Sciences, Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Mitochondrial DNA B Resour. 2019 Jul 12;4(2):2266-2280. doi: 10.1080/23802359.2019.1627921.
Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease. In our previous investigations, we have reported the spectrum and frequency of mitochondrial , and gene in Chinese LHON population. This study aimed to assess the molecular epidemiology of mutations in Chinese families with LHON. A cohort of 352 Chinese Han probands lacking the known LHON-associated mtDNA mutations and 376 control subjects underwent molecular analysis of mtDNA. All variants were evaluated for evolutionary conservation, structural and functional consequences. Fifteen variants were identified in the gene by mitochondrial genome analysis of LHON pedigrees, which was substantially higher than that of individuals from general Chinese populations. The incidences of the two known LHON-associated mutations, m.15927G > A and m.15951A > G, were 2.27% and 1.14%, respectively. Nine putative LHON-associated variants were identified in 20 probands, translated into 2.1% cases of this cohort. Moreover, mtDNAs in 41 probands carrying the mutation(s) were widely dispersed among nine Eastern Asian haplogroups. Our results suggest that the gene is a mutational hotspot for these 352 Chinese families lacking the known LHON-associated mutations. These data further showed the molecular epidemiology of mutations in Chinese Han LHON pedigrees.
Leber遗传性视神经病变（LHON）是一种母系遗传的眼病。在我们之前的研究中，我们已经报道了中国LHON人群中线粒体、和基因的谱系及频率。本研究旨在评估中国LHON家系中突变的分子流行病学。对352名缺乏已知LHON相关线粒体DNA（mtDNA）突变的中国汉族先证者和376名对照受试者进行了mtDNA分子分析。对所有变异进行了进化保守性、结构和功能后果评估。通过对LHON家系的线粒体基因组分析，在基因中鉴定出15个变异，这一数量显著高于普通中国人群个体中的变异数量。两个已知的LHON相关突变，即m.15927G＞A和m.15951A＞G的发生率分别为2.27%和1.14%。在20名先证者中鉴定出9个推定的LHON相关变异，占该队列病例的2.1%。此外，携带该突变的41名先证者的mtDNA广泛分布在9个东亚单倍群中。我们的结果表明，对于这352个缺乏已知LHON相关突变的中国家系，基因是一个突变热点。这些数据进一步展示了中国汉族LHON家系中突变的分子流行病学情况。
