TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

Autor:	Tian WT; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China., Zhan FX; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Liu ZH; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China., Liu Z; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Laboratory of Clinical Genetics, Medical Science Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China., Liu Q; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China., Guo XN; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, Dalian, China., Zhou ZW; Shanghai Xunyin Biotechnology Co., Ltd., Shanghai, China., Wang SG; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Liu XR; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Institute of Neuroscience of The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Jiang H; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China., Li XH; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Zhao GH; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China., Li HY; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Anyang People's Hospital, Anyang, China., Tang JG; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China., Bi GH; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Dongying People's Hospital, Dongying, China., Zhong P; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China., Yin XM; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China., Liu TT; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The First Hospital Affiliated to Anhui University of Science & Technology, Huainan, China., Ni RL; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The First Hospital Affiliated to Anhui University of Science & Technology, Huainan, China., Zheng HR; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The First Hospital Affiliated to Anhui University of Science & Technology, Huainan, China., Liu XL; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China., Qian XH; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Wu JY; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China., Cao YW; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China., Zhang C; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China., Liu SH; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China., Wu YY; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China., Wang QF; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China., Xu T; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China., Hou WZ; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China., Li ZY; Shanghai Jiao Tong University School of Medicine, Shanghai, China., Ke HY; Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zhu ZY; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China., Zheng L; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China., Wang T; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China., Rong TY; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Shidong Hospital of Yangpu District, Shanghai, China., Wu L; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zhang Y; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Fang K; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China., Wang ZH; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Guangdong 999 Brain Hospital, Guangzhou, China., Zhang YK; Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China., Zhang M; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, The First Hospital Affiliated to Anhui University of Science & Technology, Huainan, China., Zhao YW; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China., Tang BS; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China., Luan XH; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China., Huang XJ; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Cao L; Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.; China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.; Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China.; Department of Neurology, The First Hospital Affiliated to Anhui University of Science & Technology, Huainan, China.
Jazyk:	angličtina
Zdroj:	Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2022 Mar; Vol. 37 (3), pp. 545-552. Date of Electronic Publication: 2021 Nov 24.
DOI:	10.1002/mds.28865
Abstrakt:	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. (© 2021 International Parkinson and Movement Disorder Society.)
Databáze:	MEDLINE
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