睡眠相关过度运动性癫痫家系的基因突变与临床分析  

Analysis of gene mutations and clinical features about a sleep-related hypermotor epilepsy family

作　　者：熊建蓉 陈翔[2] XIONG Jianrong;CHEN Xiang(The Fourth Affiliated Hospital of Medical College of Zhejiang University,Department of rehabilitation medicine,Yiwu 322000,China;The Second Affiliated Hospital of Wenzhou Medical University,Department of Child Rehabilitation Medicine,Wenzhou 325027,China)

机构地区：[1]浙江大学医学院附属第四医院康复医学科,义乌322000 [2]温州医科大学附属第二医院儿童康复科,温州325027

出　　处：《癫痫杂志》2021年第6期481-491,共11页Journal of Epilepsy

摘　　要：目的旨在为解释基因型与表型的联系提供可能,为临床上睡眠相关过度运动性癫痫(Sleeprelated hypermotor epilepsy,SHE)患者的治疗提供参考。方法回顾性分析2017年12月于温州医科大学附属第二医院门诊确诊为SHE的患儿(患者1)病例资料,并询问患者1的家族史及生长发育史,得知患儿的父亲(患者2)有癫痫病史,同样采集患者2病史及生长发育史。对2例患者进行体格检查,完善脑电图、头部磁共振成像(MRI)、智力评估及血常规、血生化等基本化验检查。对确诊后的患者1和患者2均进行药物治疗,并对其疗效进行随访。此外,我们采集了患者1及其父母的外周血,对其进行基因测序,对所检出的突变基因,建立了系统进化树,并进行了同源蛋白序列比对,以判断突变的保守性。另外,利用in silico分析,对突变基因对应的致病性进行了分析。结果分析发现了一个癫痫家族,患儿和其父亲患病,临床表现不典型,均于睡眠中发作。对两者药物治疗的随访中发现,患者1和患者2对药物反应性良好。基因检查提示患者1和患者2在DEPDC5(c.484-1del c.484_485del)和KCNQ2(c.1164A>T)同一位点突变,且该突变均为首次报道。此外,同源蛋白对比序列显示两突变基因对应的氨基酸均为高度保守。结论本研究主要报道了一个睡眠相关过度运动性癫痫家系,患者1和患者2均有DEPDC5和KCNQ2基因的新发突变。本研究长期的随访中发现患者对药物治疗有效。Objective To provide the possibility to explain the relationship between genotype and phenotype,and to provide reference for the clinical treatment of Sleep-related hypermotor epilepsy(SHE).Methods We retrospectively analyzed the case data of the child(patient 1)diagnosed with SHE in the outpatient department of the Second Affiliated Hospital of Wenzhou Medical University in December 2017,and inquired about his family history and growth and development history.We learned that the father(patient 2)of the child had a history of epilepsy,and we also collected his medical history and growth and development history of patient 2.We carried out the basic physical examination for the two patients,and basic blood routine and blood biochemical indicators have also been done.In addition,electroencephalogram,Wechsler intelligence assessment and cranial magnetic resonance imaging were performed.After the diagnosis of patients 1 and 2,we treated them with antiepileptic drugs and make them long-term follow-up.What’more,we collected the peripheral blood of patient 1 and his father and mother,sequenced the gene,established phylogenetic tree for the mutation gene,and compared the homologous protein sequence to judge the conservation of the mutation.Moreover,in silico analysis was used to analyze the pathogenicity of the mutant gene.Results We find a family with epilepsy,of whom patient 1 and his father are with epilepsy.Their clinical manifestations are atypical,and their seizures are all in sleep.After a long-term follow-up of two patients'drug treatments,it is found that patient 1 and patient 2 respond well to the drugs.Gene test shows that the mutations of DEPDC5(c.484-1del c.484_485del)and KCNQ2(c.1164A>T)are at the same site in both patient 1 and patient 2,and the mutation sites are first reported.What’more,the homologous protein alignment shows that the amino acids corresponding to the two mutant genes are highly conserved.Conclusion This study mainly reports a family with sleep-related hypermotor epilepsy.Patients 1 and

关 键 词：癫痫 睡眠 治疗 基因突变 

分 类 号：R742.1[医药卫生—神经病学与精神病学]