Cheng-Yuan Mao1, Chang-He Shi1, Bo Song1, Jun Wu1, Yan Ji1, Jie Qin1, Yu-Sheng Li1, Jing-Jing Wang1, Dan-Dan Shang1, Shi-Lei Sun1, Yu-Ming Xu2. 1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000 Henan, People's Republic of China. 2. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000 Henan, People's Republic of China. Electronic address: xuyuming@zzu.edu.cn.
Abstract
BACKGROUND: Recently, PRRT2 gene mutations have been identified as a causative factor of paroxysmal kinesigenic dyskinesia (PKD). However, evidence is still lacking with respect to the genotype to phenotype correlation in PKD patients. METHODS: We recruited a cohort of PKD patients with or without PRRT2 mutations for the study, and followed them for 6 months to observe the response to carbamazepine treatment. RESULTS: Thirty-four participants were included in this study; 16 patients were positive for a hot-spot p.R217Pfs 8 heterozygous PRRT2 gene mutation, while the other 18 patients were negative for PRRT2 gene mutations. PRRT2 mutations were found to be associated with a younger age of onset, bilateral presence and a higher frequency of attacks. Furthermore, the follow-up study revealed that p.R217Pfs 8-positive patients showed dramatic improvement with complete abolition of dyskinetic episodes with carbamazepine treatment, while only 7 of the 18 patients without PRRT2 mutations showed a response to the antiepileptic drug. CONCLUSIONS: Our study indicated that positivity for PRRT2 mutation is a predictor of younger age of onset and more frequent of attacks in PKD patients. Interestingly, the presence of PRRT2 mutations also predicted a good response to carbamazepine therapy, especially at low dose. Therefore, genetic testing shows potential clinical significance for guiding the choice of medication for individual PKD cases.
BACKGROUND: Recently, PRRT2 gene mutations have been identified as a causative factor of paroxysmal kinesigenic dyskinesia (PKD). However, evidence is still lacking with respect to the genotype to phenotype correlation in PKDpatients. METHODS: We recruited a cohort of PKDpatients with or without PRRT2 mutations for the study, and followed them for 6 months to observe the response to carbamazepine treatment. RESULTS: Thirty-four participants were included in this study; 16 patients were positive for a hot-spot p.R217Pfs 8 heterozygous PRRT2 gene mutation, while the other 18 patients were negative for PRRT2 gene mutations. PRRT2 mutations were found to be associated with a younger age of onset, bilateral presence and a higher frequency of attacks. Furthermore, the follow-up study revealed that p.R217Pfs 8-positive patients showed dramatic improvement with complete abolition of dyskinetic episodes with carbamazepine treatment, while only 7 of the 18 patients without PRRT2 mutations showed a response to the antiepileptic drug. CONCLUSIONS: Our study indicated that positivity for PRRT2 mutation is a predictor of younger age of onset and more frequent of attacks in PKDpatients. Interestingly, the presence of PRRT2 mutations also predicted a good response to carbamazepine therapy, especially at low dose. Therefore, genetic testing shows potential clinical significance for guiding the choice of medication for individual PKD cases.
Authors: Alice R Gardiner; Fatima Jaffer; Russell C Dale; Robyn Labrum; Roberto Erro; Esther Meyer; Georgia Xiromerisiou; Maria Stamelou; Matthew Walker; Dimitri Kullmann; Tom Warner; Paul Jarman; Mike Hanna; Manju A Kurian; Kailash P Bhatia; Henry Houlden Journal: Brain Date: 2015-11-23 Impact factor: 13.501