SMC1A基因截短变异致儿童晚发性丛集性癫痫发作1例并文献复习

Late-onset cluster seizures caused by a truncation variation in SMC1A gene:a case report and literature revie

目的总结SMC1A基因截短变异患儿的临床表型和基因型特点。方法回顾性分析郑州大学附属儿童医院2021年2月收治并确诊的1例SMC1A基因截短变异致晚发性丛集性癫痫发作患儿的临床资料,总结其临床特征并进行文献复习。结果先证者为女性,5岁首次癫痫发作,呈丛集性发作,对多种抗癫痫药物反应差,起病前智力运动及语言发育正常。行全外显子基因组测序示:SMC1A基因存在新发杂合无义变异c.55C>T,p.Gln19Ter(p.Gln19*),该变异未见报道。共检索到相关文献14篇,结合本例共32例SMC1A基因截短变异患者,均为女性,其中30例为早发性难治性癫痫患者,首次癫痫发作中位年龄5个月(范围4周至40个月),78.1%(25/32)有丛集性发作,93.8%(30/32)合并智力发育障碍,68.8%(22/32)德朗热综合征临床评分≥4分。基因变异类型:31例为新发变异;32例中移码变异16例,无义变异12例[其中c.2923C>T位点变异3例(9.4%,3/32)],剪切变异4例。结论本研究进一步扩展了SMC1A基因截短变异的临床表型和基因型;女性晚发性丛集性癫痫发作表型少见,国内尚未见相关报道;基因检测有助于遗传性癫痫疾病的早期诊断及精准治疗。

Objective To summarize the clinical phenotype and genotypic characteristics of children with truncation variation in SMC1A gene.Methods The clinical data of a child with late-onset cluster seizures caused by truncation variation in SMC1A gene diagnosed in February 2021 in Children's Hospital Affiliated to Zhengzhou University were collected.The relevant literature was reviewed to summarize the clinical characteristics.Results The proband was a 5-year-old girl,presenting with first seizure at the age of 5 and cluster seizures.She had poor response to multiple antiepileptic drugs,and had normal neurodevelopment before seizures.Whole exome sequencing results revealed a spontaneous heterozygous nonsense variation c.55C>T in SMC1A gene,causing a nonsense variant in the amino acid sequence p.Gln19Ter(p.Gln19*),which has not been reported.There were a total of 14 relevant literatures,and there were in total 32 cases with truncation variation in SMC1A gene including this case.All children were female and 30 children had early-onset intractable epilepsy,and first seizure median age was 5 months(range:4 weeks to 40 months);78.1%(25/32)of them had cluster seizures;93.8%(30/32)had mental retardation;Cornelia de Lange syndrome clinical score in 68.8%(22/32)of them was≥4.The truncation variations in SMC1A gene of 31 children were de novo,and there were 16 children with frameshift variation(16/32),12 children with nonsense variation[12/32;3 children(9.4%,3/32)with c.2923C>T],4 children with splice variation(4/32).Conclusions This study further expands the clinical phenotype and genotype of cases with truncation variation in SMC1A gene.Case presenting with female late-onset cluster seizures has not been reported in China,and genetic testing can be beneficial for early diagnosis of hereditary epilepsy and precision treatment.