Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy
Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy
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华裔多系统萎缩患者COQ2基因突变扫描
DOI：
10.1016/j.neurobiolaging.2014.09.010
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发表时间：
2015-02-01
影响因子：
4.2
通讯作者：
Shang, Hui-Fang
中科院分区：
文献类型：
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作者：
Chen, Yong Ping;Zhao, Bi;Shang, Hui-Fang
多系统萎缩症（MSA）是一种病因不明的致命性神经退行性疾病。它被广泛认为是一种非遗传性疾病，但越来越多的证据表明，多个基因与 MSA 相关。最近，据报道，辅酶 Q2 4-羟基苯甲酸聚异戊二烯基转移酶 (COQ2) 基因的功能受损变异会增加家族性和散发性日本患者患 MSA 的风险。在本研究中，我们调查了COQ2的突变谱，并分析了COQ2外显子7中常见变异Val393Ala与中国人群MSA之间的关联。本研究纳入了四川大学华西医院神经内科的 312 名散发性 MSA 患者。对所有患者的 COQ2 的所有 7 个外显子和 598 名健康对照 (HC) 的外显子 7 进行了直接测序。通过直接测序在 300 个 HC 中证实了新的候选突变和变异。在 4 名患者中发现了两种新的非同义变异，包括 p.R173H 和 p.N386I，以及报道的错义变异 p.L162F（2 名患者中发现了 p.R173H）。然而，在上述4例患者中未检测到Val393Ala变异。 13 名 MSA 患者 (4.17%) 和 18 名对照者 (3.01%) 具有 COQ2 杂合变异 (Val393Ala/NM)。 Val393Ala 的基因型频率和次要等位基因频率在患者和对照之间或以小脑性共济失调为主的 MSA 组和帕金森病组之间不存在显着差异。中国MSA人群中COQ2的突变频率为1.28%。 COQ2 中常见的变异 Val393Ala 似乎与华人 MSA 无关。 (C) 2015 Elsevier Inc. 保留所有权利。
Multiple-system atrophy (MSA) is a fatal neurodegenerative disorder with unknown etiology. It is widely considered to be a nongenetic disorder, but accumulating evidence suggests that several genes are linked to MSA. Recently, functionally impaired variants in the coenzyme Q2 4-hydroxybenzoate polyprenyltransferase (COQ2) gene have been reported to increase the risk of MSA in familial and sporadic Japanese patients. In this study, we investigated the mutation spectrum of COQ2 and analyzed the association between the common variant Val393Ala in exon 7 of COQ2 and MSA in a Chinese population. This study included 312 sporadic MSA patients from the Department of Neurology, West China Hospital of Sichuan University. All 7 exons of COQ2 in all the patients and exon 7 in 598 healthy controls (HCs) were directly sequenced. Novel candidate mutations and variations were confirmed by direct sequencing in 300 HCs. Two novel nonsynonymous variants, including p.R173H and p.N386I, and a reported missense variant, p.L162F, were found in 4 patients (p.R173H in 2 patients). However, the Val393Ala variant was not detected in the above 4 patients. Thirteen MSA patients (4.17%) and 18 controls (3.01%) had the heterozygous variant (Val393Ala/NM) of COQ2. No significant differences existed in the genotype frequency and minor allele frequency of Val393Ala between patients and controls or between MSA characterized predominantly by cerebellar ataxia and by pakinsonism groups. The mutation frequency of COQ2 is 1.28% in a Chinese MSA population. The common variant Val393Ala in COQ2 does not appear to be associated with MSA in ethnic Chinese. (C) 2015 Elsevier Inc. All rights reserved.