关键词: 癫痫；　PRRT2基因；　突变

Abstract: Objective　To retrospectively analyze the clinical and genetic characteristics of PRRT2-associated paroxysmal diseases in children, and to improve the understanding of genotype-phenotype association of PRRT2 gene. Methods　The clinical data and genetic results of 15 infant epilepsy or paroxysmal dyskinesia patients with PRRT2 mutations were collected from neurology department of Shanghai Children’s Medical Center between May 2016 to July 2018. Results　A total of 15 patients including 8 males and 7 females were collected . The age at onset ranged from 3 months to 13 months and the median age of onset was 6 months. Thirteen patients presented focal seizures with or without secondary generalization, 1 patient presented infant spasms, and 1 patient had seizures at the age of 8 months and presented paroxysmal dyskinesia at the age of 15 years. Twelve patients had familial histories of paroxysmal diseases. Interictal electroencephalograms of 12 patients were normal, interictal electroencephalograms showed epileptiform discharges in 2 cases, atypical peak arrhythmias were observed in 1 patient. MRI tests were normal in 12 patients and showed deepen cerebral sulcus in 2 patients. Fourteen patients were well controlled after using antiepileptic drugs but 1 patient had recurrence after drug withdrawal, and 1 patient was resistant to antiepileptic drugs. All patients had PRRT2 heterozygous mutations, including 9 cases of duplication mutations (c.649dupC, p.Arg217Profs*8） , 2 cases of missense mutations (c.439G>C, p.Asp147His; c.640G>C, p.Ala214Pro; c.962T>C, p.Leu321Pro), 2 cases of deletion mutations (c.649delC, p.Arg217Glufs*12; c.650delG，p.Arg217Glnfs12*), 2 cases of nonsense mutation (c.649C>T, p.Arg217*; c.970G>T, p.Gly324*). Among these mutations, two were novel mutations （c.962T>C and c.970G>T）. In 15 cases, 13 cases inherited mutations from one of parent, 2 cases were de novo mutation. Eleven patients were diagnosed as benign familial infant epilepsy (BFIE), 2 patients were diagnosed as benign infant epilepsy (BIE), 1 patient was diagnosed as paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) and 1 patient was diagnosed as infant spasms. Conclusions　The most common clinical phenotype of PRRT2 gene mutation in pediatrics is BFIE, followed by BIE and PKD/IC. C.649 dupC is the hotspot mutation of PRRT2 gene, and c.962T > C, c.970G > T are likely pathogenic mutations.

Key words: 　epilepsy;　PRRT2 gene;　mutation