Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.

Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.

Cell reports (2012-07-27)

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 Gurnett, Edouard 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

PMID22832103

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.