Novel PRRT2 mutations in paroxysmal dyskinesia patients with variant inheritance and phenotypes. (21st December 2012)

• Record Type: Journal Article
• Authors: Liu, X.‐R.; Wu, M.; He, N.; Meng, H.; Wen, L.; Wang, J.‐L.; Zhang, M.‐P.; Li, W.‐B.; Mao, X.; Qin, J.‐M.; Li, B.‐M.; Tang, B.; Deng, Y.‐H.; Shi, Y.‐W.; Su, T.; Yi, Y.‐H.; Tang, B.‐S.; Liao, W.‐P.
• Is Part Of: Genes, brain, and behavior. Volume 12:Number 2(2013:Mar.)
• Page Start: 234
• Page End: 240
• Publication Date: 2012-12-21
• Subjects: Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12008
• Languages: English
• ISSNs: 1601-1848

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>Paroxysmal dyskinesias (PDs) are a group of episodic movement disorders with marked variability in clinical manifestation and potential association with epilepsy. <italic>PRRT2</italic> has been identified as a causative gene for PDs, but the phenotypes and inheritance patterns of <italic>PRRT2</italic> mutations need further clarification. In this study, 10 familial and 21 sporadic cases with PDs and PDs‐related phenotypes were collected. Genomic DNA was screened for <italic>PRRT2</italic> mutations by direct sequencing. Seven <italic>PRRT2</italic> mutations were identified in nine (90.0%) familial cases and in six (28.6%) sporadic cases. Five mutations are novel: two missense mutations (c.647C>G/p.Pro216Arg and c.872C>T/p.Ala291Val) and three truncating mutations (c.117delA/p.Val41TyrfsX49, c.510dupT/p.Leu171SerfsX3 and c.579dupA/p.Glu194ArgfsX6). Autosomal dominant inheritance with incomplete penetrance was observed in most of the familial cases. In the sporadic cases, inheritance was heterogeneous including recessive inheritance with compound heterozygous mutations, inherited mutations with incomplete parental penetrance and <italic>de novo</italic> mutation. Variant phenotypes associated with <italic>PRRT2</italic> mutations, found in 36.0% of the affected cases, included febrile convulsions, epilepsy, infantile non‐convulsive seizures (INCS) and nocturnal convulsions (NC). All patients with INCS or NC, not reported previously, displayed abnormalities on electroencephalogram (EEG). No EEG abnormalities were recorded in patients with classical infantile convulsions and paroxysmal choreoathetosis (ICCA)/paroxysmal kinesigenic dyskinesia (PKD). Our study further confirms that <italic>PRRT2</italic> mutations are the most common cause of familial PDs, displaying both dominant and recessive inheritance. Epilepsy may occasionally occur in ICCA/PKD patients with <italic>PRRT2</italic> mutations. Variant phenotypes INCS or NC differ from classical ICCA/PKD clinically and electroencephalographically. They have some similarities with, but not identical to epilepsy, possibly represent an overlap between ICCA/PKD and epilepsy</bold>.</p> </abstract>