TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large‐Sample Study

ABSTRACTBackgroundParoxysmal 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.ObjectiveWe aimed to explore the potential causative gene for PKD.MethodsA 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.ResultsTransmembrane 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.ConclusionsWe 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

Topics

No keywords indexed for this article. Browse by subject →

References

28

[1]

10.1002/mds.28061

[2]

10.1212/01.wnl.0000147298.05983.50

[3]

10.1016/j.neurol.2016.07.005

[4]

10.1212/wnl.0b013e3182661fe3

[5]

10.1093/brain/awr289

[6]

10.1038/ng.1008

[7]

10.1093/brain/awv317

[8]

10.1002/mds.27274

[9]

10.1002/ana.24580

[10]

10.1007/s00702-021-02335-x

[11]

10.1016/j.seizure.2018.02.005

[12]

10.1093/hmg/ddx430

[13]

10.1093/brain/awy073

[14]

10.1038/s41419-021-03569-z

[15]

10.1002/1531-8257(200005)15:3<429::aid-mds1001>3.0.co;2-r

[16]

10.1016/j.neuron.2010.10.008

[17]

10.1212/wnl.0000000000002079

[18]

10.1016/j.jns.2015.02.046

[19]

10.1177/1550059416662575

[20]

10.1186/s13059-018-1579-x

[21]

TMEM151A variants cause paroxysmal kinesigenic dyskinesia

Hong-Fu Li, Yu-lan Chen, Ling Zhuang et al.

Cell Discovery 10.1038/s41421-021-00322-w

[22]

10.1186/s40035-021-00231-8

[23]

REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants

Nilah M. Ioannidis, Joseph H. Rothstein, Vikas Pejaver et al.

The American Journal of Human Genetics 10.1016/j.ajhg.2016.08.016

[24]

10.1007/s10072-013-1408-7

[25]

10.3389/fneur.2018.00831

[26]

10.3390/ijms21103603

[27]

10.1016/j.parkreldis.2012.02.006

[28]

10.1007/s00018-015-2052-6

Cited By

30

TMEM151A in forebrain excitatory neurons negatively regulates seizure susceptibility

Hui‐Wen Zhou, Bin Lu · 2025

Epilepsia

Heterozygous KCNJ10 Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia

Xiaojun Huang, Xin Fu · 2024

Movement Disorders

Genetic and phenotypic analyses of PRRT2 positive and negative paroxysmal kinesigenic dyskinesia

Yingying Zhang, Jiechuan Ren · 2024

Therapeutic Advances in Neurologica...

TMEM151A variants associated with paroxysmal kinesigenic dyskinesia

Hua lin Huang, Qing xia Zhang · 2023

Human Genetics

Metrics

30

Citations

28

References

Details

Published: Nov 24, 2021
Vol/Issue: 37(3)
Pages: 545-552
License: View

Authors

W

Wo‐Tu Tian

Department of Neurology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China; China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China

F

Fei‐Xia Zhan

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

Z

Zhen‐Hua Liu

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Xiangya Hospital Central South University Changsha China

Z

Zhe Liu

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

Q

Qing Liu

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

X

Xia‐Nan Guo

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

Z

Zai‐Wei Zhou

Shanghai Xunyin Biotechnology Co., Ltd. Shanghai China

S

Shi‐Ge Wang

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

X

Xiao‐Rong Liu

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Institute of Neuroscience of The Second Affiliated Hospital of Guangzhou Medical University Guangzhou China

H

Hong Jiang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Xiangya Hospital Central South University Changsha China

X

Xun‐Hua Li

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, The First Affiliated Hospital Sun Yat‐sen University Guangzhou China

G

Guo‐Hua Zhao

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, The Fourth Affiliated Hospital Zhejiang University School of Medicine Yiwu China

H

Hai‐Yan Li

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Anyang People's Hospital Anyang China

J

Jian‐Guang Tang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, The Second Xiangya Hospital Central South University Changsha China

G

Guang‐Hui Bi

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Dongying People's Hospital Dongying China

P

Ping Zhong

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Suzhou Hospital of Anhui Medical University Suzhou China

X

Xiao‐Meng Yin

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Xiangya Hospital Central South University Changsha China

T

Tao‐Tao Liu

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology The First Hospital Affiliated to Anhui University of Science & Technology Huainan China

R

Rui‐Long Ni

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology The First Hospital Affiliated to Anhui University of Science & Technology Huainan China

H

Hao‐Ran Zheng

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology The First Hospital Affiliated to Anhui University of Science & Technology Huainan China

X

Xiao‐Hang Qian

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

J

Jing‐Ying Wu

Department of Neurology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China; China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China

Y

Yu‐Wen Cao

Department of Neurology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China; China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China

C

Chao Zhang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Suzhou Hospital of Anhui Medical University Suzhou China

S

Shi‐Hua Liu

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Suzhou Hospital of Anhui Medical University Suzhou China

Y

Ying‐Ying Wu

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Suzhou Hospital of Anhui Medical University Suzhou China

Q

Qun‐Feng Wang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Suzhou Hospital of Anhui Medical University Suzhou China

T

Ting Xu

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Suzhou Hospital of Anhui Medical University Suzhou China

W

Wen‐Zhe Hou

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Suzhou Hospital of Anhui Medical University Suzhou China

Z

Zi‐Yi Li

Shanghai Jiao Tong University School of Medicine Shanghai China

H

Hui‐Yi Ke

Shanghai Jiao Tong University School of Medicine Shanghai China

Z

Ze‐Yu Zhu

Department of Neurology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China; China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China

L

Lan Zheng

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Minhang Hospital Fudan University Shanghai China

T

Tian Wang

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

T

Tian‐Yi Rong

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Shidong Hospital of Yangpu District Shanghai China

L

Li Wu

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Y

Yu Zhang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

K

Kan Fang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Shanghai General Hospital Shanghai Jiao Tong University Shanghai China

Z

Zhan‐Hang Wang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology Guangdong 999 Brain Hospital Guangzhou China

Y

Ya‐Kun Zhang

Department of Laboratory Medicine, Zhongshan Hospital Fudan University Shanghai China

M

Mei Zhang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology The First Hospital Affiliated to Anhui University of Science & Technology Huainan China

Y

Yu‐Wu Zhao

Department of Neurology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China; China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China

B

Bei‐sha Tang

China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China; Department of Neurology, Xiangya Hospital Central South University Changsha China

X

Xing‐Hua Luan

Department of Neurology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China; China Paroxysmal Dyskinesia Collaborative Group (CPDCG) Shanghai China

X

Xiao‐Jun Huang

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

L

Li Cao

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

Funding

National Natural Science Foundation of China Award: 81870889

Health and Family Planning Commission of Sichuan Province Award: 20184Y0056

Cite This Article

Wo‐Tu Tian, Fei‐Xia Zhan, Zhen‐Hua Liu, et al. (2021). TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large‐Sample Study. Movement Disorders, 37(3), 545-552. https://doi.org/10.1002/mds.28865

TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large‐Sample Study

You May Also Like