Novel ATP13A2 and PINK1 variants identified in Chinese patients with Parkinson's disease by whole-exome sequencing
Novel ATP13A2 and PINK1 variants identified in Chinese patients with Parkinson's disease by whole-exome sequencing
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DOI：
10.1016/j.neulet.2020.135075
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发表时间：
2020-08-10
影响因子：
2.5
通讯作者：
Wu, Zhi-Ying
中科院分区：
文献类型：
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作者：
Chen, Hui;Jin, Yu-Hua;Wu, Zhi-Ying
遗传因素被认为在早发性帕金森病（EOPD）患者中发挥着关键作用。 EOPD 患者的遗传谱已在白种人群体中进行了广泛的研究，但在中国人群中却很少。在这项研究中，共有 21 名无亲属关系的中国 EOPD 患者入组。进行多重连接依赖性探针扩增测定和全外显子组测序，然后进行桑格测序。提出了详细的临床特征。两个新的可能致病变异（ATP13A2 中的 p.Q648X 和 PINK1 中的 p.N521fs）和 10 个先前报道的 Parkin 致病变异（外显子 2 缺失、外显子 3-4 缺失、外显子 4 缺失、外显子 6-7 缺失、外显子 7 缺失；p.G284R、p.G329 V、p.R366W、p.N428fs、 p.M458 L) 在 21 名患者中的 9 名 (42.86%) 中被鉴定出。我们的队列中 Parkin 变异的频率 (33.33%) 远高于东亚人群。携带 ATP13A2 变异的患者对左旋多巴治疗没有反应。我们的研究结果拓宽了 EOPD 患者的遗传谱和临床特征。
Genetic factors are considered to play a critical role in patients with early-onset Parkinson's disease (EOPD). The genetic spectrum of EOPD patients has been extensively investigated in Caucasian populations but rarely in the Chinese population. In this study, a total of 21 unrelated Chinese EOPD patients were enrolled. Multiplex ligation-dependent probe amplification assay and whole-exome sequencing were performed, followed by Sanger sequencing. Detailed clinical features were presented. Two novel likely pathogenic variants (p.Q648X in ATP13A2 and p.N521fs in PINK1) and 10 previously reported Parkin pathogenic variations (exon 2 deletion, exon 3-4 deletion, exon 4 deletion, exon 6-7 deletion, exon 7 deletion; p.G284R, p.G329 V, p.R366W, p.N428fs, p.M458 L) were identified in 9 out of 21 (42.86%) patients. The frequency (33.33%) of Parkin variations is much higher in our cohort than that in the East Asian population. The patient carrying the ATP13A2 variant showed no response to levodopa treatment. Our findings broaden the genetic spectrum and clinical features of EOPD patients.