Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

被引：247

作者：

Lee, Hsien-Yang ^{[1
]}

Huang, Yong ^{[1
,2
]}

Bruneau, Nadine ^{[3
]}

Roll, Patrice ^{[4
]}

Roberson, Elisha D. O. ^{[5
]}

Hermann, Mark ^{[1
]}

Quinn, Emily ^{[1
,2
]}

Maas, James ^{[1
]}

Edwards, Robert ^{[1
]}

Ashizawa, Tetsuo ^{[6
]}

Baykan, Betul ^{[7
]}

Bhatia, Kailash ^{[8
]}

Bressman, Susan ^{[9
]}

Bruno, Michiko K. ^{[1
,10
]}

Brunt, Ewout R. ^{[11
]}

Caraballo, Roberto ^{[12
]}

Echenne, Bernard ^{[13
]}

Fejerman, Natalio ^{[12
]}

Frucht, Steve ^{[14
]}

Gurnett, Christina A. ^{[15
]}

Hirsch, Edouard ^{[16
]}

Houlden, Henry ^{[8
]}

Jankovic, Joseph ^{[17
]}

Lee, Wei-Ling ^{[18
]}

Lynch, David R. ^{[19
]}

Mohammed, Shehla ^{[20
]}

Mueller, Ulrich ^{[21
]}

Nespeca, Mark P. ^{[22
]}

Renner, David ^{[23
]}

Rochette, Jacques ^{[24
]}

Rudolf, Gabrielle ^{[16
]}

Saiki, Shinji ^{[25
]}

Soong, Bing-Wen ^{[26
,27
]}

Swoboda, Kathryn J. ^{[23
]}

Tucker, Sam ^{[19
]}

Wood, Nicholas ^{[8
]}

Hanna, Michael ^{[8
]}

Bowcock, Anne M. ^{[5
]}

Szepetowski, Pierre ^{[3
]}

Fu, Ying-Hui ^{[1
]}

Ptacek, Louis J. ^{[1
,2
]}

机构：

[1] UCSF, Dept Neurol, San Francisco, CA 94158 USA

[2] Howard Hughes Med Inst, San Francisco, CA 94158 USA

[3] Univ Aix Marseille 2, INSERM, Inst Neurobiol Mediterranee, INMED U901, F-13273 Marseille 9, France

[4] Univ Aix Marseille 2, INSERM, UMR S910, F-13385 Marseille 05, France

[5] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA

[6] Univ Florida, Dept Neurol, Gainesville, FL 32611 USA

[7] Istanbul Univ, Istanbul Fac Med, Dept Neurol, TR-34390 Istanbul, Turkey

[8] UCL, Inst Neurol, London WC1N 3BG, England

[9] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA

[10] Queens Med Ctr, Dept Neurol, Honolulu, HI 96813 USA

[11] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, NL-9713 GZ Groningen, Netherlands

[12] Juan P Garrahan Pediat Hosp, Dept Neurol, RA-1245 Buenos Aires, DF, Argentina

[13] Hop Gui De Chauliac, Serv Neuropediat, F-34295 Montpellier, France

[14] Mt Sinai Med Ctr, Movement Disorders Ctr, New York, NY 10029 USA

[15] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[16] Hop Univ Strasbourg, Serv Neurol, F-67091 Strasbourg, France

[17] Baylor Coll Med, Parkinsons Dis Ctr & Movement Disorders Clin, Dept Neurol, Houston, TX 77030 USA

[18] Natl Inst Neurosci, Singapore 308433, Singapore

[19] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA

[20] Guys Hosp, Clin Genet, London SE1 9RT, England

[21] Univ Giessen, Inst Humangenet, D-35392 Giessen, Germany

[22] Univ Calif San Diego, Rady Childrens Hosp San Diego, Dept Neurosci, Div Pediat Neurol, San Diego, CA 92123 USA

[23] Univ Utah, Dept Neurol, Salt Lake City, UT 84132 USA

[24] Univ Picardie Jules Verne, INSERM, UMR 925, Serv Genet, F-80036 Amiens, France

[25] Kanazawa Med Univ, Dept Neurol, Kanazawa, Ishikawa 9200293, Japan

[26] Natl Yang Ming Univ, Sch Med, Dept Neurol, Taipei 11221, Taiwan

[27] Taipei Vet Gen Hosp, Neurol Inst, Dept Neurol, Taipei 11221, Taiwan

来源：

CELL REPORTS | 2012年 / 1卷 / 01期

关键词：

HUMAN-CHROMOSOME; 16; DYSTONIC CHOREOATHETOSIS; LINKAGE; 16P12-Q12; LOCUS; GLUT1; CONFIRMATION; EXOCYTOSIS; FAMILIES; SUGGESTS;

D O I：

10.1016/j.celrep.2011.11.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

引用

页码：2 / 12

页数：11

共 44 条

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