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

Hsien Yang Lee, Yong Huang, Nadine Bruneau, Patrice Roll, Elisha D.O. Roberson, Mark Hermann, Emily Quinn, James Maas, Robert Edwards, Tetsuo Ashizawa, Betul Baykan, Kailash Bhatia, Susan Bressman, Michiko K. Bruno, Ewout R. Brunt, Roberto Caraballo, Bernard Echenne, Natalio Fejerman, Steve Frucht, Christina A. GurnettEdouard Hirsch, Henry Houlden, Joseph Jankovic, Wei Ling Lee, David R. Lynch, Shehla Mohammed, Ulrich Müller, Mark P. Nespeca, David Renner, Jacques Rochette, Gabrielle Rudolf, Shinji Saiki, Bing Wen Soong, Kathryn J. Swoboda, Sam Tucker, Nicholas Wood, Michael Hanna, Anne M. Bowcock, Pierre Szepetowski, Ying Hui Fu, Louis J. Ptáček

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2-12
Number of pages11
JournalCell Reports
Volume1
Issue number1
DOIs
StatePublished - Jan 26 2012

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    Lee, H. Y., Huang, Y., Bruneau, N., Roll, P., Roberson, E. D. O., Hermann, M., Quinn, E., Maas, J., Edwards, R., Ashizawa, T., Baykan, B., Bhatia, K., Bressman, S., Bruno, M. K., Brunt, E. R., Caraballo, R., Echenne, B., Fejerman, N., Frucht, S., ... Ptáček, L. J. (2012). Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions. Cell Reports, 1(1), 2-12. https://doi.org/10.1016/j.celrep.2011.11.001