PRRT2 c.649dupC Mutation Derived from De Novo in Paroxysmal Kinesigenic Dyskinesia

Aims PRRT2 was recently identified as a causative gene for paroxysmal kinesigenic dyskinesia (PKD), and the c.649dupC mutation was shown to be a high frequency mutation. This mutation was also identified in many sporadic cases. This might be attributed to the incomplete penetrance of c.649dupC. Alternatively, c.649dupC might derive from de novo. The aim of this study is to elucidate the possibility concerning de novo mutagenesis of PRRT2 mutations in PKD. Methods Nine sporadic Chinese PKD patients including one Mongolian patient were recruited. Direct sequencing of PRRT2 was performed in them and their parents. Haplotype analysis was conducted to confirm the biological relationship. Results A novel mutation, c.133_136delCCAG, was identified in one Han patient and his unaffected mother. The c.649dupC mutation was detected in another Han patient and his unaffected father. To our interest, c.649dupC was detected in the Mongolian patient but not in his parents. Haplotype analysis confirmed the biological relationship among the trio. No mutations were identified in the remaining six patients. Conclusion These findings demonstrate the heterogeneity of PKD, and the de novo mutagenesis of PRRT2 gene might indicate the genetic instability of this region.