摘要目的 研究婴儿惊厥伴阵发性舞蹈手足徐动症(infantile convulsions with paroxysmal choreoathetosis,ICCA)的临床表型和富脯氨酸跨膜蛋白2(proline-rich transmenbrane protein 2,PRRT2)基因突变特点.方法 收集ICCA患者及其家系成员的临床资料及外周血DNA,对受累者的临床表型进行分析;采用PCR和Sanger测序的方法筛查PRR T2基因突变.结果 共收集11个ICCA家系和1例散发的ICCA患者.11个家系中共有49例受累者,其中15例仅表现为婴儿期惊厥;18例仅表现为阵发性运动诱发的运动障碍(paroxysmal kinesigenic dyskinesia,PKD);16例先后出现婴儿期惊厥和PKD.婴儿期惊厥起病年龄为3～12个月,PKD起病年龄为5～17岁,其中2个家系中共有4例受累者伴有偏头痛.1例散发ICCA患儿生后3个半月～4个月出现无热抽搐,3岁9个月出现发作性肢体扭动,4岁10个月开始服奥卡西平,运动障碍症状完全控制.11个ICCA家系均发现有PRR T2基因突变,其中突变c.649_650insC(p.R217PfsX8)最常见,占总突变的54.5％(6/11).1例ICCA散发病例发现有PRR T2基因突变(c.649_650insC),且证实为新生突变.结论 ICCA家系中PKD症状的发病年龄在儿童期或青少年期,少数家系的部分受累者可出现偏头痛;PRR T2是ICCA的致病基因,其中突变c.649_650insC是PRRT2基因的热点突变;PRR T2基因突变也可见于ICCA散发病例.

abstractsObjective To analyze the phenotypes and proline-rich transmenbrane protein 2 (PRRT2) gene mutations in patients of infantile convulsions with paroxysmal choreoathetosis (ICCA).Methods Clinical data were collected from ICCA patients and their family members.Genomic DNA was extracted from peripheral blood samples with standard protocol.Mutations of PRRT2 were screened using PCR amplification and Sanger sequencing.Results Eleven families and one sporadic case with ICCA were recruited in this study.In 11 ICCA families,49 family members were affected,of which 15 individuals had benign infantile convulsions (BIC) alone,18 individuals had only paroxysmal kinesigenic dyskinesia(PKD),and 16 individuals had BIC followed by PKD.The seizure onset age of infantile convulsions was between 3 and 12 months.The onset age of PKD was ranging from 5 to 17 years old.Four affected members in two ICCA families had PKD or ICCA co-existing with migraine.The one sporadic ICCA case had afebrile seizures between 3.5 and 4 months,and developed paroxysmal twists of limbs after 3 years and 9 months of age.He had good response to treatment with oxcarbazepine at the age of 4 years and 10 months.PRRT2 mutations were identified in all 11 ICCA families.The most common mutation,c.649 _650insC (p.R217PfsX8),was detected in 6 of the 11 families (54.5％).PRRT2 mutation (c.649_650insC) was also found in the sporadic ICCA case,and was identified as de novo mutation.Conclusion The phenotype of PKD in ICCA families occurred in childhood or adolescence.Few affected members in some ICCA families may have migraine.PRRT2 is the causative gene of ICCA and the mutation c.649_650insC was the hotspot of PRRT2 mutations.PRRT2 mutation was also found in sporadic case with ICCA.