PRRT2 mutation in Korean patients with paroxysmal kinesigenic dyskinesia: A clinico-genetic analysis

Background & Objective: Recently, mutations in PRRT2 have been found to cause paroxysmal kinesigenic dyskinesia (PKD). However, only several reports have described the detailed clinical features of patients with the PRRT2 mutation compared to those without the mutation. Furthermore, 16p11.2 microdeletions including PRRT2 also have been reported in patients with PKD; however, it is unknown to what extent the PRRT2 deletion contributes to the development of PKD. Methods: We performed mutation screening in 29 Korean patients with PKD analyzing the sequence and gene dosage of PRRT2 and their clinical features. Results: Overall, genetic abnormalities in PRRT2 were identified in 7 patients (24%): 3 from the 6 familial cases (50%) and 4 from the 23 sporadic cases (17%). The previously reported c.649dupC and c.649delC were found in 5 and 1 patient, respectively, and a novel mutation c.323_324delCA was found in 1 patient. No patients had deletions involving the PRRT2 gene. Compared with the mutation-negative cases, the age of PKD onset was earlier in the mutation-positive cases. However, there were no differences in the other clinical features. A dystonia-only phenotype was reported only in the mutation-negative cases. Contrary to common belief that patients with PKD have an excellent response to carbamazepine, 3 mutation-positive patients taking carbamazepine reported only a partial response. Conclusions: PRRT2 is a common causative gene for Korean patients with PKD. Our results show that the incomplete response to carbamazepine does not exclude the PRRT2 mutation. Neurology Asia 2014; 19(4) : 357 – 362 Address correspondence to: Beom S. Jeon, Department of Neurology, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea. Tel: +82-2-2072-2876, Fax: +82-2-3672-7553, e-mail: [email protected] INTRODUCTION Paroxysmal dyskinesias are characterized by recurrent attacks of involuntary movements such as choreoathetosis or dystonia. Both familial and sporadic forms exist, and they can be classified into three categories: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD) and paroxysmal exerciseinduced dyskinesia (PED), among which PKD is the most common. Recently, it has been found that mutations in PRRT2 cause PKD and infantile convulsions with choreoathetosis, an allelic disorder of PKD, in many ethnic groups. Subsequently, PRRT2 mutations have been implicated in other paroxysmal disorders including PNKD, PED, episodic ataxia, hemiplegic migraine, and migraine with aura suggesting a wide clinical spectrum associated with PRRT2 mutations. In addition, 16p11.2 microdeletions including the PRRT2 gene also have been reported in patients with PKD. However, it is unknown to what degree the PRRT2 deletion contributes to the development of PKD. In this study, we performed mutation screening in 29 Korean patients with PKD analyzing the sequence and gene dosage of PRRT2 and their clinical features. Neurology Asia December 2014