FOXG1相关综合征3例患儿临床及基因检测结果分析  

Analysis of clinical and genetic detection results of 3 children with FOXG1-related syndrome

作　　者：孙殿荣 王岩艳 李加山 张雷红 候梅 SUN Dianrong;WANG Yanyan;LI Jiashan;ZHANG Leihong;HOU Mei(Department of Children Rehabilitation,Women and Children's Hospital Affiliated to Qingdao University,Qingdao 266011,Shandong,China;Department of Children Healthcare,Women and Children's Hospital Affiliated to Qingdao University,Qingdao 266011,Shandong,China;Department of Children Genetics,Women and Children's Hospital Affiliated to Qingdao University,Qingdao 266011,Shandong,China)

机构地区：[1]青岛大学附属妇女儿童医院儿童康复中心,山东青岛266011 [2]青岛大学附属妇女儿童医院儿保科,山东青岛266011 [3]青岛大学附属妇女儿童医院遗传科,山东青岛266011

出　　处：《临床儿科杂志》2024年第9期805-810,共6页Journal of Clinical Pediatrics

基　　金：青岛市出生缺陷与罕见病临床医学研究中心项目(No.22-3-7-1 czx-1-nsh);青岛市医药卫生科研计划(No.2021-WJZD130);国家临床重点专科建设项目-儿科学(No.XKRC-012)。

摘　　要：目的分析FOXG1相关综合征的临床表型与基因型特点。方法回顾性分析2018年1月至2022年1月收治的FOXG1相关综合征患儿的临床资料及遗传学检测结果。结果纳入3例FOXG1相关综合征患儿,均为男性,生后起病,均有早发性运动障碍、全面性发育迟缓、产后小头畸形的表现。全外显子组测序发现3例患儿均具有FOXG1基因致病性变异。颅脑磁共振成像(MRI)特点为额叶皮层和/或胼胝体发育不良或髓鞘化延迟。例1为FOXG1基因N-末端结构域位点c.256dupC(p.Gln 86 Profs*35)移码突变,例2为FOXG1基因叉头结合域c.595G>T(p.Glu 199*)无义突变,例3为FOXG1基因JARID1B结合域c.1178C>A(p.S 393*)无义突变,例3临床表型和脑部异常改变轻于其他2例患儿。其中例2和例3患儿的突变之前未见文献报道,扩展了该疾病的基因变异谱。结论对于有早发性运动障碍、发育迟缓、小头畸形和特异性颅脑影像学表现的个体,应考虑FOXG1基因变异的可能。Objective To investigate the clinical phenotypic and genotypic features of FOXG1-related syndrome.Methods The clinical data and genetic test results of 3 children with FOXG1-related syndrome treated in our hospital from January 2018 to January 2022 were analyzed retrospectively.Results Three children with FOXG1-related syndrome were included,all male,with postnatal onset.All the patients had early-onset dyskinesia,global developmental delay and microcephaly.Whole exome sequencing showed that all 3 patients had the pathogenic variation of FOXG1 gene.Brain magnetic resonance imaging(MRI)was characterized by hypoplasia of the frontal cortex and/or corpus callosum or delayed myelination.Case 1 had a frameshift mutation of c.256 dupC(p.Gln 86 Profs*35)at the N-terminal domain site in the FOXG1 gene,and case 2 had a nonsense mutation of c.595 G>T(p.Glu 199*)in the fork-head binding domain of FOXG1 gene.A nonsense of c.1178 C>A(p.S 393*)was found in the JARID 1 B binding domain of FOXG1 gene in case 3.Case 3 had a milder clinical phenotype and brain abnormalities than the other 2 patients.The variations of cases 2 and 3 had not been previously reported in the literature,which expanded the gene spectrum of the disease.Conclusions FOXG1 variation should be considered for individuals with early-onset dyskinesia,developmental delay,microcephaly and characteristic brain imaging lesions.

关 键 词：FOXG1基因 运动障碍 发育迟缓 小头畸形 

分 类 号：R725.9[医药卫生—儿科]