Coding mutations in NUS1 contribute to Parkinson’s disease

作者：Jifeng Guo, Lu Zhang, Kai Li, Junpu Mei, Jin Xue, Jia Chen, Xia Tang, Lu Hua Shen, Hong Feng Jiang, Chao Chen, Hui Guo, Xueli Wu, Silong Sun, Qian Xu, Qiying Sun, Piu Chan, Huifang Shang, Tao Wang, Guohua Zhao, Jing-yu Liu, Xue-feng Xie, Yiqi Jiang, Zhenhua Liu, Yuwen Zhao, Zuobin Zhu, Jia‐Da Li, Zhengmao Hu, Xinxiang Yan, Xiaodong Fang, Guanghui Wang, Fengyu Zhang, Kun Xia, Chunyu Liu, Xiongwei Zhu, Zhenyu Yue, Shuai Cheng Li, Huaibin Cai, Zhuohua Zhang, Ranhui Duan, Beisha Tang · 发表于：Proceedings of the National Academy of Sciences · 年份：2018 · DOI：10.1073/pnas.1809969115 · 被引用次数：96 · 研究领域：CRISPR and Genetic Engineering、Genomics and Chromatin Dynamics、Studies on Chitinases and Chitosanases

Significance Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world. Several common and rare genetic risk variants associated with PD pathogenesis have been identified, predominantly in persons of European descent, but the genetic contributions to familial PD are largely unknown for Han Chinese. Here, we present a trio-based study to explore the association between de novo-altered genes and early onset PD in Han Chinese. We found that the 12 genes with de novo mutations were biologically connected to each other and likely to be disease-risk genes. Further analyses using two independent cohorts revealed that NUS1 harbored more rare nonsynonymous variants, and subsequent functional studies on Drosophila proved its potential link to PD pathogenesis.