Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A
Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A
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DOI：
10.1016/j.mrfmmm.2008.06.004
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发表时间：
2008-08-25
影响因子：
2.3
通讯作者：
Zhang, Ya-Ping
中科院分区：
文献类型：
--
作者：
Wang, Hua-Wei;Jia, Xiaoyun;Zhang, Ya-Ping
Leber遗传性视神经病变（LHON）在原发性线粒体DNA（mtDNA）突变家系中的发病率非常复杂。母系和核遗传背景，以及环境因素，已被报道参与不同的影响家系。本文报道两个LHON家系，其患病率分别为53.3%和15.0%（P < 0.02）。对这两个家族的完整mtDNA基因组的分析显示，存在主要突变G11778 A和其他几个变体，表明相同的单倍群状态G2 a。具有较高的突变率的家族包含先前描述的二级突变G13708 A，其在正常中国样本中呈现多态性，并且不影响体内线粒体氧化代谢，如先前的研究所述。进化分析未发现与G11778 A共分离的脓毒症致病突变。我们的研究结果表明，LHON在两个中国家庭中的可变突变率是独立的mtDNA单倍型背景和继发突变G13708 A。因此，可能是未知的核基因参与和/或其他因素导致了LHON的显著不同的突变率。(c)2008 Elsevier B. V.保留所有权利。
The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate any putatively pathogenic mutation that cosegregated with G11778A in these two pedigrees. Our results suggest that the variable penetrance of LHON in the two Chinese families is independent of both their mtDNA haplotype background and a secondary mutation G13708A. As a result, it is likely that unknown nuclear gene involvement and/or other factors contribute to the strikingly different penetrance of LHON. (c) 2008 Elsevier B.V. All rights reserved.