摘要
目的对1例癫痫伴全面性发育落后患儿的临床特征及ZBTB18基因变异进行分析,明确其可能的致病原因,为临床诊断提供依据。方法选择四川大学华西第二医院确诊的1例癫痫伴全面性发育落后患儿,分析其临床表现、实验室检查及ZBTB18基因变异。结果患儿主要表现为全面性发育落后、身材矮小、癫痫发作;脑电图示睡眠期右侧中央区尖(慢)波多次发放,睡眠期额、右侧后颞区尖波偶见发放;头颅MRI示未见明显异常。全外显子测序显示ZBTB18基因(OMIM:608433)存在杂合变异c.1282;283del(p.Phe428LeufsTer72),根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,c.1282;283del判定为可能致病性变异(PS2+PVS1;oderate+PM2;upporting)。对目前报道的28例ZBTB18基因变异患儿的临床表型及基因型进行分析,运动发育迟缓、语言发育落后及癫痫3类临床表型在ZBTB18基因移码/无义变异,错义变异两组患者中差异具有统计学意义(P≤0.05)。结论ZBTB18基因c.1282;283del变异可能为患儿的致病原因,基因检测结果为患儿的临床诊断提供了依据。移码/无义变异较错义变异可能更容易出现运动发育迟缓、语言发育落后。
Objective To analyze the clinical characteristics and ZBTB18 gene variant in a child with epilepsy and global developmental delay.Methods Clinical data and laboratory examination of the patient were reviewed.Whole exome sequencing(WES)was also carried out for the family trio.Results The main manifestations of the child included global developmental delay,short stature,epileptic seizures.EEG revealed frequent occurrence of sharp(slow)waves in the right central region during sleeping,with sharp waves occasionally seen in the frontal and right posterior temporal regions.Cranial MRI has shown no obvious abnormality.WES has identified a de novo pathogenic variant in the ZBTB18 gene[NM_205768.3:exon 2:c.1282_1283del(p.Phe428Leufs*72)].Based on the guidelines from American College of Medical Genetics and Genomics(ACMG),the variant was classified as pathogenic(PS2+PVS1_Moderate+PM2_Supporting).Following treatment with levetiracetam and rehabilitation,the seizures have been controlled for nearly half a year,with improvement of the psychomotor and language development.So far 28 children have been discovered with ZBTB18 gene mutations,and there was a significant difference in the clinical phenotypes of motor retardation,language retardation and epilepsy between those harboring frameshift/nonsense mutations and missense mutations.Conclusion The c.1282_1283del(p.Phe428leufs*72)variant of the ZBTB18 probably underlay the autosomal dominant mental disorder type 22 in this child.Compared with missense mutations,frameshift/nonsense mutations may predispose more to motor retardation,delayed language development and epilepsy.
作者
张佳
李杨
罗欢
沈亚君
袁梦
杨作臻
甘靖
Zhang Jia;Li Yang;Luo Huan;Shen Yajun;Yuan Meng;Yang Zuozhen;Gan Jing(Department of Pediatrics,West China Second Hospital,Sichuan University,Chengdu,Sichuan 610041,China;Key Laboratory of Obstetric&Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education,Sichuan University,Chengdu,Sichuan 610041,China;Cipher Gene LLC,Beijing 100089,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第3期293-296,共4页
Chinese Journal of Medical Genetics
基金
国家自然科学基金(82071686,81501301)
四川省科技厅重点研发项目(2021YFS0093)
2020年度四川大学华西第二医院"临床科研基金"(KL115,KL072)。
