Clinico-genetic comparisons of paroxysmal kinesigenic dyskinesia patients with and without PRRT2 mutations

Background and purpose: Mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many detailed clinico-genetic correlations have been performed. Methods: To investigate PRRT2 mutations in a mixed Asian PKD population and perform clinico-genetic correlations, we recruited patients between 2002 and 2011 and administered a standardized questionnaire. Results: Amongst 29 unrelated patients with PKD recruited, five PRRT2 mutations were present in 15 patients. Three mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs; c.697_698delAG/p.Ser233Trp fsX5). Clinico-genetic correlations revealed that a history of seizures was more common in patients with PRRT2 mutations, although this did not reach statistical significance (P= 0.08). A younger age of onset, non-Chinese, and the presence of premonitory sensations were significantly associated with PRRT2 mutations in the univariate analysis. Multivariate logistic regression analysis demonstrated that age of onset [odds ratio (OR)=0.59, P=0.025] and premonitory sensation (OR=10.67, P=0.028) were independently associated with positive PRRT2 mutation. Conclusions: PRRT2 mutations are common in patients with PKD, and a double PRRT2 mutation is reported for the first time. PRRT2 mutations are significantly associated with a younger age of onset and the presence of premonitory sensation in our population.