良性家族性婴儿癫痫家系临床表型和PRRT2基因突变分析

Phenotypes and PRRT2 mutation analysis in families with benign familial infantile epilepsy

目的 探讨良性家族性婴儿癫痫（BFIE）家系的临床表型和编码富脯氨酸跨膜蛋白2的基因PRRT2的突变特点.方法 2006年9月至2013年8月在北京大学第一医院儿科神经专业门诊收集BFIE先证者及其家系成员的临床资料及外周血DNA;对家系受累者的临床表型进行分析;采用PCR和Sanger测序的方法筛查PRRT2基因突变.结果 收集的29个BFIE家系中,共有110例受累者,起病年龄为2 ～12个月,中位起病年龄为4.5个月.先证者癫痫发作均有丛集性发作特点,2例先证者分别在生后25和31个月时出现腹泻诱发的抽搐发作1次.在4个BFIE家系中,共有4例成员有热性惊厥病史.29个BFIE家系中,17个家系发现有PRRT2基因突变,突变检出率为58.6％ （17/29）,其中12个家系突变为c.649_650insC（p.R217PfsX8）,3个家系突变为c.649delC（p.R217EfsX12）,其余2个家系突变分别为c.323 _324delCA（p.T108SfsX25）和c.904_905insG（p.D302GfsX39）.结论 BFIE家系中受累者癫痫发作的起病年龄最小为2个月,多有丛集性发作特点.PRRT2是我国BFIE家系的主要致病基因,其中突变c.649_650insC为PRRT2的热点突变,突变c.323_324delCA为首次在BFIE家系中发现的新突变.少数携带PRRT2基因突变者可出现热性惊厥表型.

Objective To study the phenotypes and proline-rich transmembrane protein 2 （PRRT2） mutations in families with benign familial infantile epilepsy （BFIE）.Method Data of all BFIE probands and their family members were collected from Peking University First Hospital between September 2006 and August 2013.Clinical phenotypes of affected members were analyzed.Genomic DNA was extracted from peripheral blood samples with standard protocol.Mutations in PRRT2 were screened using PCR amplification and Sanger sequencing.Result Twenty-nine BFIE families were recruited in this study.In total,110 family members were affected.The age of seizure onset of these affected members was between 2 and 12 months （median：4.5 months）.All probands presented with clusters of seizures.Two probands had one seizure induced by diarrhea respectively at 25 months and 31 months.In four BFIE families,four family members had a history of febrile seizures.PRRT2 mutations were found in 17 of the 29 （58.6％） BFIE families.Mutation c.649_650insC was detected in 12 of the 17 families with PRRT2 mutations.Mutation c.649delC （p.R217EfsXl2） was identified in three families.Mutation c.323_324delCA （p.T108SfsX25） and c.904_905insG （p.D302GfsX39） were detected in one family,respectively.Conclusion The minimum seizure onset age of affected members in BFIE families was 2 months of age.The seizures often occur in clusters.PRRT2 is the major causative gene of BFIE in Chinese families.Mutation c.649_650insC is the hotspot mutation of PRRT2.A novel mutation c.323_324delCA was first reported in BFIE family.Few affected members with PRRT2 mutation presented with febrile seizures phenotype.