摘要
目的探讨5例SCN8A基因变异所致癫痫患儿的临床及遗传学特点。方法收集2015年8月至2022年8月在临沂市人民医院拟诊为遗传性癫痫患儿的临床资料,对其进行家系全外显子组测序,对候选变异进行Sanger测序家系验证。结果共筛选出5例(4男1女)携带SCN8A变异的患儿。患儿1具有良性家族性婴儿癫痫,携带遗传自父亲(具有相似表型)的c.4840A>G变异,为已报道致病性变异。患儿2~4为中间型癫痫。患儿2携带c.3967G>A新发变异,根据美国医学遗传学与基因组学学会(ACMG)相关指南评级为致病性变异(PS1+PS2+PM1+PM2Supporting+PP3),患儿3携带c.415A>T变异,患儿4携带c.4697C>T新发变异,均评级为可能致病性变异(PS2+PM1+PM2Supporting+PP3)。患儿5具有早期婴儿癫痫性脑病,之后转变为类Lennox-Gastaut综合征,携带c.5615G>A新发变异,为已报道致病性变异。5例患儿的首次发病年龄为2~14个月,均存在局灶性发作和全面强直阵挛发作,患儿1、2、3、5具有丛集性发作的特点,患儿1~4单药或双药治疗后发作得到控制,生长发育正常,患儿5属于药物难治性癫痫,且存在严重的发育落后。结论上述5例癫痫患儿均存在成簇发作、良性癫痫成年期偶尔发作、中间型癫痫停药易复发的新特点,SCN8A基因变异考虑为其致病原因。
Objective To explore the clinical and genetic characteristics of five children with epilepsies due to variants of SCN8A gene.Methods Clinical data of five children(four males and one female)admitted to Linyi People′s Hospital due to hereditary epilepsies between August 2015 and August 2022 were collected.Whole exome sequencing was carried out for these children,and candidate variants were verified by Sanger sequencing.Results All of the five children were found to harbor variants of the SCN8A gene.Case 1,who had benign familial infantile epilepsy,inherited a known pathogenic c.4840A>G variant from his father with similar symptoms.Cases 2 to 4 had presented with intermediate epilepsy.Among these,case 2 has harbored a de novo c.3967G>A variant which was rated as pathogenic(PS1+PS2+PM1+PM2_Supporting+PP3)based on the guidelines from the American College of Medical Genetics and Genomics.Cases 3 and 4 were found to respectively harbor a de novo c.415A>T and a c.4697C>T variant,which were both rated as likely pathogenic(PS2+PM1+PM2_Supporting+PP3).Case 5,who had early-onset infantile epileptic encephalopathy transformed into Lennox Gastaut-like syndrome,has harbored a de novo c.5615G>A variant,which was known to be pathogenic.The children had their age of onset ranging from 2 to 14 months,and all had focal seizures and generalized tonic clonic seizures.Four children(cases 1,2,3 and 5)had cluster seizures,four(cases 1 to 4)had become seizure-free after single or dual treatment and showed normal growth and development,whilst case 5 was drug-resistant and showed severe developmental retardation.Conclusion The five children had new features such as cluster seizures,occasional benign seizures in adulthood,and intermediate epilepsy which are prone to relapse after discontinuation of medication,which may be attributed to the pathogenic variants of the SCN8A gene.
作者
张新
邱世彦
杨莉
李玉芬
徐那
余西西
Zhang Xin;Qiu Shiyan;Yang Li;Li Yufen;Xu Na;Yu Xixi(Postgraduate Training Base of Jinzhou Medical University,Linyi People's Hospital,Linyi,Shandong 276003,China;Linyi People's Hospital,Linyi,Shandong 276003,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2024年第2期174-180,共7页
Chinese Journal of Medical Genetics
基金
山东省医药卫生科技发展计划(2018W399)。
