CAJ | 학술논문

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.
목적 탐토량성가족성영인전간(BFIE)가계적림상표형화편마부포안산과막단백2적기인PRRT2적돌변특점.방법 2006년9월지2013년8월재북경대학제일의원인과신경전업문진수집BFIE선증자급기가계성원적림상자료급외주혈DNA;대가계수루자적림상표형진행분석;채용PCR화Sanger측서적방법사사PRRT2기인돌변.결과 수집적29개BFIE가계중,공유110례수루자,기병년령위2 ～12개월,중위기병년령위4.5개월.선증자전간발작균유총집성발작특점,2례선증자분별재생후25화31개월시출현복사유발적추휵발작1차.재4개BFIE가계중,공유4례성원유열성량궐병사.29개BFIE가계중,17개가계발현유PRRT2기인돌변,돌변검출솔위58.6％ (17/29),기중12개가계돌변위c.649_650insC(p.R217PfsX8),3개가계돌변위c.649delC(p.R217EfsX12),기여2개가계돌변분별위c.323 _324delCA(p.T108SfsX25)화c.904_905insG(p.D302GfsX39).결론 BFIE가계중수루자전간발작적기병년령최소위2개월,다유총집성발작특점.PRRT2시아국BFIE가계적주요치병기인,기중돌변c.649_650insC위PRRT2적열점돌변,돌변c.323_324delCA위수차재BFIE가계중발현적신돌변.소수휴대PRRT2기인돌변자가출현열성량궐표형.
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.