Lee HY - Huang Y - Bruneau N - Roll P - Roberson ED - Hermann M - Quinn E - Maas J - Edwards R - Ashizawa T - Baykan B - Bhatia K - Bressman S - Bruno MK - Brunt ER - Caraballo R - Echenne B - Fejerman N - Frucht S - Gurnett CA - Hirsch E - Houlden H - Jankovic J - Lee WL - Lynch DR - Mohammed S - Müller U - Nespeca MP - Renner D - Rochette J - Rudolf G - Saiki S - Soong BW - Swoboda KJ - Tucker S - Wood N - Hanna M - Bowcock AM - Szepetowski P - Fu YH - Ptáček LJ
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.