染色体拷贝数变异相关孤独症谱系障碍伴发癫痫五例临床分析  

Clinical analysis of five cases of autism spectrum disorder complicated with epilepsy with chromosome copy number variation

作　　者：李铭玉 叶静[1] 黄朝阳[1] 林一聪[1] 刘爱华[1] 李莉萍[1] 陈佳 王玉平[1] Li Mingyu;Ye Jing;Huang Zhaoyang;Lin Yicong;Liu Aihua;Li Liping;Chen Jia;Wang Yuping(Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China)

机构地区：[1]首都医科大学宣武医院神经内科,北京100053

出　　处：《中华医学杂志》2019年第33期2615-2618,共4页National Medical Journal of China

基　　金：国家重点研发计划(2017YFC0907702).

摘　　要：目的报道5例孤独症谱系障碍伴癫痫患者的临床表现及染色体检测结果,以提高对染色体拷贝数变异相关神经精神发育障碍的认识。方法收集2017年9月至2018年9月首宣武医院收治的5例孤独症谱系障碍伴癫痫患者的临床资料,包括病史、智力水平、发育水平、体格检查、头颅影像及脑电图。通过高通量全基因组测序对5例患者及其双亲进行基因检测。结果5例孤独症合并癫痫患者,其中男4例,女1例。5例患者均有轻度的智力减退。其中1例患者有明显的生长发育迟缓及颅面部畸形。癫痫的平均起病年龄为6.3岁(7个月至16岁),发作形式主要为强直阵挛发作。5例患者服用抗癫痫药物后发作均明显减少。基因检测结果提示5例患者均携带拷贝数变异,其中3例文献报道致病性明确,2例尚未见报道,分别为染色体16p13.3重复及染色体21q22.3缺失,是新发现的拷贝数变异。结论本研究结果支持孤独症谱系障碍伴癫痫发作常与拷贝数变异相关,如Williams-Beuren区重复综合征、染色体15q11.2重复综合征及染色体15q11.2缺失综合征等。本研究在2例孤独症谱系障碍伴癫痫发作患者中发现新的拷贝数变异,分别为染色体16p13.3重复及染色体21q22.3缺失。Objective To explore the clinical features and genetic causes of autism spectrum disorder (ASD) patients with epilepsy. Methods The clinical data of five patients with ASD and epilepsy admitted to Xuanwu Hospital between September 2017 and September 2018 were collected, including medical history, intelligence level, developmental level, physical examination, neuroimaging and electroencephalogram. High-throughput whole-genome sequencing was applied to five patients and their parents. Results Of five patients, four were male and one was female. All five patients had mild mental retardation, and one patient had significant growth retardation and craniofacial deformity. The average epilepsy onset age was 6.3 years old (7 months to 16 years). The main epileptic type was tonic-clonic seizure with abnormal EEG results. All patients have a favorable response to anti-epileptic drugs. Whole-exome sequencing (WES) revealed copy number variation in all 5 patients. Among them, 3 cases were reported to be pathogenic, and 2 cases were not reported (chromosome 16p13.3 duplication and chromosome 21q22.3 deletion). Conclusions The results of current study support that autism spectrum disorders with seizures is often associated with copy number variations, such as Williams-Beuren region duplication syndrome, chromosome 15q11.2 duplication syndrome and chromosome 15q11.2 deletion syndrome. We reported two novel copy number variations (chromosome 16p13.3 duplication and chromosome 21q22.3 deletion) in two autism spectrum disorder patients with epileptic seizures.

关 键 词：孤独症谱系障碍 拷贝数变异 癫痫 

分 类 号：R749.94[医药卫生—神经病学与精神病学]