MICAL1基因变异所致常染色体显性遗传性颞叶外侧癫痫的临床特征及遗传学分析  

Clinical characteristics and genetic analysis of autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation

作　　者：梅道启 马昂 张兵兵[1] 师晓燕[1] 王曼丽[1] 张利亚[1] 汤继宏[1] Mei Daoqi;Ma Ang;Zhang Bingbing;Shi Xiaoyan;Wang Manli;Zhang Liya;Tang Jihong(Department of Neurology,Children′s Hospital of Soochow University,Suzhou 215025,China;Department of Pediatrics,Peking University People′s Hospital,Beijing 100044,China)

机构地区：[1]苏州大学附属儿童医院神经内科,苏州215025 [2]北京大学人民医院儿科,北京100044

出　　处：《中华神经科杂志》2025年第3期292-298,共7页Chinese Journal of Neurology

基　　金：苏州市科技计划项目(SKY2022007);疑难病、罕见病研究专项项目(2024YNHJ03)。

摘　　要：目的探讨MICAL1基因新生变异所致1例常染色体显性遗传性颞叶外侧癫痫患儿的临床特征和基因变异特点。方法回顾性分析苏州大学附属儿童医院神经内科2019年8月确诊的1例MICAL1基因新生变异所致常染色体显性遗传性颞叶外侧癫痫患儿的临床资料,总结其临床特征,对核心家系成员进行家系全外显子基因测序,并对其基因变异特点进行分析。结果先证者为10岁5个月男童,因“间断抽搐7年”就诊,临床表现为局灶性及全面强直-阵挛性发作、听觉先兆,语言及智力发育正常。3.0 T头颅磁共振平扫成像、3D头颅磁共振薄层扫描成像中T_(1)及液体衰减反转恢复序列未见异常。长程视频脑电图示左侧额、颞区棘波和棘慢波发放。核心家系成员全外显子基因测序结果提示,先证者MICAL1基因存在未见报道的新生杂合错义变异(NM_022765):c.763G>T(exon6)(p.Val255Leu),根据2015年美国医学遗传学基因组学学会和分子病理协会指南,该变异为可能致病变异。应用抗癫痫发作药物能有效控制癫痫发作。结论听觉症状为常染色体显性遗传性颞叶外侧癫痫患儿的主要临床表现,抗癫痫发作药物能有效控制患儿的癫痫发作,MICAL1基因c.763G>T(p.Val255Leu)变异是本例先证者的遗传学病因。ObjectiveTo investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICAL1 gene.MethodsClinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation diagnosed in Children′s Hospital of Soochow University in August 2019 were collected.The whole exome sequencing was performed on the core members of the family,and the characteristics of gene variations were analyzed.ResultsThe proband,a 10 years and 5 months old boy,was admitted to the hospital because of"intermittent convulsions for 7 years".The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura,with normal language and intellectual development.No abnormalities were found in the T_(1) and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thin-slice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas.The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICAL1 gene of the proband(NM_022765):c.763G>T(exon6)(p.Val255Leu)that had not been reported.According to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines(2015),the mutation was considered potentially pathogenic.The application of antiepileptic drugs was effective in controlling epileptic seizures.ConclusionsAuditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy.Antiepileptic drugs can effectively control epileptic seizures of the child,and the MICAL1 gene c.763G>T(p.Val255Leu)mutation is the genetic cause of the proband.

关 键 词：癫痫 颞叶 MICAL1基因 常染色体显性遗传 听力障碍 全外显子基因测序 

分 类 号：R742.1[医药卫生—神经病学与精神病学]