[PDF][PDF] Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions

HY Lee, Y Huang, N Bruneau, P Roll, EDO Roberson… - Cell reports, 2012 - cell.com
HY Lee, Y Huang, N Bruneau, P Roll, EDO Roberson, M Hermann, E Quinn, J Maas…
Cell reports, 2012cell.com
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 …
Summary
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.
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