PCDH19基因相关癫痫四例临床与遗传学分析

Clinical and genetic analysis of 4 cases of PCDH19 gene related epilepsy

目的 探讨PCDHl9基因突变阳性的癫痫患儿的基因型和临床表型特点。方法 收集2015年10月至2018年10月在湖南省儿童医院神经内科住院的癫痫发作具有热敏感性及从集性发作特点的女性癫痫患儿,收集患儿及其家系成员的临床资料和外周血DNA进行遗传病全外显子组基因测序。结果 4例患儿基因筛查结果均提示PCDH19基因突变阳性,均为1号外显子上的新发突变。首次发作均为发热诱发,有热敏感和丛集性的特点,发作形式多样,包括局灶性发作、全面性强直-阵挛发作及部分继发全面性发作,发作时间较短,仅1例出现过癫痫持续状态,智力发育正常或轻中度落后,其中1例可疑孤独症样表现,1例有明显好动、躁动等行为异常。结论 PCDHl9是继SCNlA之后另一个热敏感相关性癫痫的重要致病基因,以新生突变为主,发作具有热敏感和丛集性的特点,且多数发作持续时间短,1min以内,很少持续状态,常有智力发育落后,部分可有孤独症样或多动、躁动等精神行为异常表现。早期基因检测对于明确病情、判断预后及遗传咨询均至关重要。

Objective To explore the genotype and phenotype of PCDH19 gene related epilepsy. Method Clinical data of femal epilepsy manifested by fever- sensitivity and clusters, who were admitted seen at Department of Neurology of Hunan Children’s Hospital from October 2015 to October 2018,were prospectively collected. Genomic DNAs were extracted from the patients and their family members. Result PCDH19 mutations were detected in both 4 patients. The four de novo mutations were alllocated in exon 1.Onset of seizures were triggered by fever. In all patients, seizures manifested fever-sensitive and in clusters.The types of seizures include generalized tonic clonic seizure( GTCS) focal seizure and partial secondary generalized seizure. Seizures are short and only one case has a history of status convulsion. 1 case showed suspicious autistic symptoms and 1 case showed obvious hyperactivity, restlessness and other abnormal behaviors. Conclusion PCDHl9 is another important gene of epilepsy manifested by fever- sensitivity, mutations mainly occurred de novo.PCDH19 gene related epilepsy are short without status convulsion. Some can show autistic symptoms and hyperactivity, restlessness and other abnormal behaviors. Early gene testings for suspected patients is not only helpful for the clinicians to understanding and analyze the prognosis of the disease, but also important for providing genetic counseling to the parents.