Paroxysmal hypnogenic dyskinesia is associated with mutations in the PRRT2 gene.
OBJECTIVE
To explore the potential causative genes of paroxysmal hypnogenic dyskinesia (PHD), which was initially considered a subtype of paroxysmal dyskinesia and has been recently considered a form of nocturnal frontal lobe epilepsy (NFLE).


METHODS
Eleven patients with PHD were recruited. Mutations in proline-rich region transmembrane protein-2 (PRRT2), myofibrillogenesis regulator 1 (MR-1), solute carrier family 2, member 1 (SLC2A1), calcium-activated potassium channel alpha subunit (KCNMA1), cholinergic receptor, nicotinic, alpha 4 (CHRNA4), cholinergic receptor, nicotinic, beta 2 (CHRNB2), cholinergic receptor, nicotinic, alpha 2 (CHRNA2), and potassium channel subfamily T member 1 (KCNT1) were screened by direct sequencing.


RESULTS
Two PRRT2 mutations were identified in patients with typical PHD. A mutation of c.649dupC (p.Arg217ProfsX8) was identified in a patient with PHD and his father who was diagnosed with paroxysmal kinesigenic dyskinesia. An additional mutation of c.640G>C (p.Ala214Pro) was identified in a sporadic patient and his asymptomatic mother. No mutations were found in the other screened genes.


CONCLUSIONS
The present study identified PRRT2 mutations in PHD, extending the phenotypic spectrum of PRRT2 and supporting the classification of PHD as a subtype of paroxysmal dyskinesia but not NFLE. Based on the results of this study, screening for the PRRT2 mutation is recommended in patients with PHD.
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Xiao-Rong
XR
Liu
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Dan
D
Huang
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Jie
J
Wang
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Yi-Fan
YF
Wang
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Hui
H
Sun
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Bin
B
Tang
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Wen
W
Li
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Jin-Xing
JX
Lai
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Na
N
He
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Mei
M
Wu
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Tao
T
Su
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Heng
H
Meng
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Yi-Wu
YW
Shi
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Bing-Mei
BM
Li
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Bei-Sha
BS
Tang
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China (X.-R.L., D.H., J.W., Y.-F.W., H.S., B.T., W.L., J.-X.L., N.H., M.W., T.S., H.M., Y.-W.S., B.-M.L., W.-P.L.), Guangzhou, China; and Department of Neurology (B.-S.T.), Xiangya Hospital, Central South University, Changsha, China.
Wei-Ping
WP
Liao