摘要
目的探讨无脑回-巨脑回畸形患儿的临床特征及遗传病因学机制,分析其临床表型与基因型的关系。方法收集2016年10月至2017年12月在深圳市儿童医院神经内科诊治的21例无脑回-巨脑回畸形患儿的临床资料并进行随访,对所有患儿进行全基因组测序分析。结果21例患儿中伴癫痫18例(86%),不伴癫痫3例(14%);癫痫起病年龄较小,1岁以内起病16例(89%);其中单纯巨脑回畸形16例(76%),无脑回合并巨脑回畸形3例(14%),单纯无脑回畸形2例(10%)。癫痫综合征主要包括West综合征12例(67%),大田原综合征2例(11%),其他癫痫性脑病2例(11%),局灶性癫痫2例(11%)。头颅磁共振成像(MRI)提示单纯巨脑回畸形占多数,其中广泛性巨脑回畸形更多见(56%,9/16例)。全基因组测序结果:检出与无脑回-巨脑回畸形明确相关的致病/疑似致病性单核苷酸变异(SNV)/拷贝数变异(CNV)13例,检出率为62%,PAFAH1B1基因变异4例,染色体17p13.3微缺失综合征(导致PAFAH1B1整个基因缺失)6例,DCX、KIF2A、PIK3R2基因变异各1例。其中PAFAH1B1基因变异或缺失导致无脑回-巨脑回畸形占比48%(10/21例),并以顶枕叶或广泛性脑回畸形为主要改变。既往未见报道的新变异有PAFAH1B1:c.1067G>A、PAFAH1B1:c.897delT及KIF2A:c.2225delG。结论无脑回-巨脑回畸形多伴癫痫,以West综合征常见,头颅MRI提示广泛性巨脑回畸形多见。PAFAH1B1基因变异或缺失是导致无脑回-巨脑回畸形的主要原因。新变异的发现丰富了无脑回-巨脑回畸形的基因型谱数据库。
Objective To study the clinical features and molecular genetic mechanisms of children with lissencephaly(LIS),as well as to analyze the relationship between genotypes and phenotypes of the disease.Methods From October 2016 to December 2017,the clinical data and follow-ups of 21 LIS children were collected in the Department of Neurology,Shenzhen Children′s Hospital.Whole genome sequencing(WGS)was performed for genetic testing.Results Among these 21 cases,18 cases developed epilepsy(86%),and 3 cases were seizure free(14%).The onset age of children with epilepsy was relatively young,and 16 cases occurred within 1 year old(89%).Among these cases,16 were pachygyria(76%),3 cases were agyria combined with pachygyria(14%)and 2 cases were agyria(10%).Epileptic syndromes included 12 cases of West syndrome(67%),2 cases of Ohtahara syndrome(11%),2 cases of other epileptic encephalopathy(11%),and 2 cases of focal epilepsy(11%).Brain magnetic resonance imaging(MRI)demonstrated that most cases were pachygyria,among which diffuse pachygyria was more common(56%,9/16 cases).The results of WGS:13 pathogenic or likely pathogenic single nucleotide variants(SNV)and copy number variants(CNV)were detected.The total detection rate was 62%,of which 2 cases were frameshift,1 case was nonsense and 1 case was missense variants of PAFAH1B1,6 cases were chromosome 17p13.3 deletion syndrome,thus lea-ding to the whole gene deletion of PAFAH1B1,and 1 case was missense variant of DCX,frameshift variant of KIF2A,and missense variant of PIK3R2,respectively.Totally,48%(10/21 cases)of the cases were variants or deletions of PAFAH1B1,which resulted in lissencephaly in the parietal-occipital region of the brain.Novel variants were PAFAH1B1:c.1067G>A,PAFAH1B1:c.897delT and KIF2A:c.2225delG.Conclusions Most cases of LIS accompanied with epilepsy,in which West syndrome was relatively more common.Brain MRI showed that most cases were diffuse pachygyria.The variants and deletions of PAFAH1B1 was the main genetic cause of LIS.The identification of the novel variants expanded the genotypical spectrum of LIS.
作者
邹东方
廖建湘
段婧
文飞球
Zou Dongfang;Liao Jianxiang;Duan Jing;Wen Feiqiu(Department of Neurology,Shenzhen Children′s Hospital,Shenzhen 518038,Guangdong Province,China;Department of Hematology and Oncology,Shenzhen Children′s Hospital,Shenzhen 518038,Guangdong Province,China)
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2021年第9期663-668,共6页
Chinese Journal of Applied Clinical Pediatrics
基金
深圳市科技创新委员会科技应用示范项目 (KJYY20151116165726645)
深圳市医疗卫生三名工程项目 (SZSM201812005)。
