作者
Wotu Tian,Feixia Zhan,Zhenhua Liu,Zhe Liu,Qing Liu,Xia‐Nan Guo,Zaiwei Zhou,Shi‐Ge Wang,Xiao‐Rong Liu,Hong Jiang,Xunhua Li,Guohua Zhao,Haiyan Li,Jianguang Tang,Guang‐Hui Bi,Ping Zhong,Xiao‐Meng Yin,Taotao Liu,Ruilong Ni,Haoran Zheng,Li Cao,Xiao-hang Qian,Jingying Wu,Yuwen Cao,Chao Zhang,Shihua Liu,Yingying Wu,Qunfeng Wang,Ting Xu,Wenzhe Hou,Ziyi Li,Huiyi Ke,Zeyu Zhu,Lan Zheng,Tian Wang,Tian‐Yi Rong,Li Wu,Yu Zhang,Kan Fang,Zhan⁃hang WANG,Ya‐Kun Zhang,Mei Zhang,Yuwu Zhao,Beisha Tang,Xinghua Luan,Xiao‐Jun Huang,Li Cao
摘要
ABSTRACT Background Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one‐third of PKD patients are attributed to proline‐rich transmembrane protein 2 ( PRRT2 ) mutations. Objective We aimed to explore the potential causative gene for PKD. Methods A cohort of 196 PRRT2 ‐negative PKD probands were enrolled for whole‐exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case–control analysis, was applied to identify the candidate genes. Another 325 PRRT2 ‐negative PKD probands were subsequently screened with Sanger sequencing. Results Transmembrane Protein 151 ( TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A ‐related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A ‐positive and PRRT2 ‐positive groups. Conclusions We consolidated mutations in TMEM151A causing PKD with the aid of case–control analysis of a large‐scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A ‐related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A ‐related PKD. © 2021 International Parkinson and Movement Disorder Society