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.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Mar 10;39(3):293-296. doi: 10.3760/cma.j.cn511374-20210630-00556.
To analyze the clinical characteristics and ZBTB18 gene variant in a child with epilepsy and global developmental delay.
Clinical data and laboratory examination of the patient were reviewed. Whole exome sequencing (WES) was also carried out for the family trio.
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.
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.
分析1例癫痫伴全面发育迟缓患儿的临床特征及ZBTB18基因变异情况。
回顾患儿的临床资料及实验室检查结果。对患儿及其父母进行全外显子组测序（WES）。
患儿主要表现为全面发育迟缓、身材矮小、癫痫发作。脑电图显示睡眠时右侧中央区频繁出现尖（慢）波，额区及右侧后颞区偶见尖波。头颅磁共振成像未见明显异常。WES检测发现ZBTB18基因存在一个新发的致病变异[NM_205768.3：外显子2：c.1282_1283del（p.Phe428Leufs*72）]。根据美国医学遗传学与基因组学学会（ACMG）指南，该变异被分类为致病性变异（PS2+PVS1_Moderate+PM2_Supporting）。给予左乙拉西坦治疗及康复训练后，癫痫发作已控制近半年，精神运动及语言发育有所改善。目前已发现28例ZBTB18基因突变患儿，移码/无义突变患儿与错义突变患儿在运动迟缓、语言发育迟缓及癫痫等临床表型上存在显著差异。
ZBTB18基因的c.1282_1283del（p.Phe428leufs*72）变异可能是该患儿常染色体显性遗传性精神障碍22型的病因。与错义突变相比，移码/无义突变可能更易导致运动迟缓、语言发育延迟及癫痫。
