Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology in Taizhou Municipal Hospital, Taizhou, China.
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology in Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
Neurosci Lett. 2020 Aug 10;733:135075. doi: 10.1016/j.neulet.2020.135075. Epub 2020 May 22.
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.
遗传因素被认为在早发性帕金森病（EOPD）患者中起着关键作用。EOPD 患者的遗传谱在白种人群体中得到了广泛研究，但在中国人中很少研究。在这项研究中，共纳入了 21 名无血缘关系的中国 EOPD 患者。进行了多重连接依赖性探针扩增检测和全外显子组测序，随后进行了 Sanger 测序。呈现了详细的临床特征。在 9 名（42.86%）患者中发现了 2 种新的可能致病变异（ATP13A2 中的 p.Q648X 和 PINK1 中的 p.N521fs）和 10 种先前报道的 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.M458L）。携带 ATP13A2 变异的患者对左旋多巴治疗没有反应。我们的发现拓宽了 EOPD 患者的遗传谱和临床特征。
