FOXG1相关综合征3例患儿临床及基因检测结果分析
收稿日期: 2023-11-07
网络出版日期: 2024-09-04
基金资助
青岛市出生缺陷与罕见病临床医学研究中心项目(22-3-7-1czx-1-nsh);青岛市医药卫生科研计划(2021-WJZD130);国家临床重点专科建设项目-儿科学(XKRC-012)
Analysis of clinical and genetic detection results of 3 children with FOXG1-related syndrome
Received date: 2023-11-07
Online published: 2024-09-04
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.Gln86Profs*35)移码突变,例2为FOXG1基因叉头结合域c.595G>T(p.Glu199*)无义突变,例3为FOXG1基因JARID1B结合域c.1178C>A(p.S393*)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。
孙殿荣 , 王岩艳 , 李加山 , 张雷红 , 候梅 . FOXG1相关综合征3例患儿临床及基因检测结果分析[J]. 临床儿科杂志, 2024 , 42(9) : 805 -810 . DOI: 10.12372/jcp.2024.23e1074
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.256dupC (p.Gln86Profs*35) at the N-terminal domain site in the FOXG1 gene, and case 2 had a nonsense mutation of c.595G>T (p.Glu199*) in the fork-head binding domain of FOXG1 gene. A nonsense of c.1178C>A (p.S393*) was found in the JARID1B 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.
Key words: FOXG1gene; movement disorder; developmental delay; microcephaly
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