论著

FOXG1相关综合征3例患儿临床及基因检测结果分析

  • 孙殿荣 ,
  • 王岩艳 ,
  • 李加山 ,
  • 张雷红 ,
  • 候梅
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  • 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)

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

  • Dianrong SUN ,
  • Yanyan WANG ,
  • Jiashan LI ,
  • Leihong ZHANG ,
  • Mei HOU
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  • 1. Department of Children Rehabilitation, Women and Children's Hospital Affiliated to Qingdao University, Qingdao 266011, Shandong, China
    2. Department of Children Healthcare, Women and Children's Hospital Affiliated to Qingdao University, Qingdao 266011, Shandong, China
    3. Department of Children Genetics, Women and Children's Hospital Affiliated to Qingdao University, Qingdao 266011, Shandong, China

Received date: 2023-11-07

  Online published: 2024-09-04

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.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。

本文引用格式

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

Abstract

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.

参考文献

[1] Shoichet SA, Kunde SA, Viertel P, et al. Haploinsufficiency of novel FOXG1B variants in a patient with severe mental retardation, brain malformations and microcephaly[J]. Hum Genet, 2005, 117(6): 536-544.
[2] Mencarelli MA, Kleefstra T, Katzaki E, et al. 14q12 Microdeletion syndrome and congenital variant of Rett syndrome[J]. Eur J Med Genet, 2009, 52(2-3): 148-152.
[3] Lee-Chin Wong, Yen-Tzu Wu, Chia-Jui Hsu, et al. Cognition and evolution of movement disorders of FOXG1-related syndrome[J]. Front Neurol, 2019, 10: 641.
[4] Akol I, Gather F, Vogel T. Paving Therapeutic avenues for FOXG1 syndrome: untangling genotypes and phenotypes from a molecular perspective[J]. Int J Mol Sci, 2022, 23(2): 954.
[5] Wong LC, Huang CH, Chou WY, et al. The clinical and sleep manifestations in children with FOXG1 syndrome[J]. Autism Res, 2023, 16(5): 953-966.
[6] Kortüm F, Das S, Flindt M, et al. The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis[J]. J Med Genet, 2011, 48(6): 396-406.
[7] Mitter D, Pringsheim M, Kaulisch M, et al. FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants[J]. Genet Med, 2018, 20(1): 98-108.
[8] Bjerregaard VA, Levy AM, Batz MS, et al. Involvement of mitochondrial dysfunction in FOXG1 syndrome[J]. Genes (Basel), 2023, 14(2): 246.
[9] Dai S, Li J, Zhang H, et al. Structural basis for DNA recognition by FOXG1 and the characterization of disease-causing FOXG1 Mutations[J]. J Mol Biol, 2020, 432(23): 6146-6156.
[10] Wilpert NM, Marguet F, Maillard C, et al. Human neuropathology confirms projection neuron and interneuron defects and delayed oligodendrocyte production and maturation in FOXG1 syndrome[J]. Eur J Med Genet, 2021, 64(9): 104282.
[11] Yu B, Liu J, Su M, et al. Disruption of Foxg1 impairs neural plasticity leading to social and cognitive behavioral defects[J]. Mol Brain, 2019, 12(1): 63.
[12] Brimble E, Reyes KG, Kuhathaas K, et al. Expanding genotype-phenotype correlations in FOXG1 syndrome: results from a patient registry[J]. Orphanet J Rare Dis, 2023, 18(1): 149.
[13] Caporali C, Signorini S, De Giorgis V, et al. Early-onset movement disorder as diagnostic marker in genetic syndromes: three cases of FOXG1-related syndrome[J]. Eur J Paediatr Neurol, 2018, 22(2): 336-339.
[14] Wong LC, Singh S, Wang HP, et al. FOXG1-related syndrome: from clinical to molecular genetics and pathogenic mechanisms[J]. Int J Mol Sci, 2019, 20(17): 4176.
[15] Vegas N, Cavallin M, Maillard C, et al. Delineating FOXG1 syndrome: from congenital microcephaly to hyperkinetic encephalopathy[J]. Neurol Genet, 2018, 4(6): e281.
[16] Iwayama H, Tanaka T, Aoyama K, et al. Regional difference in myelination in monocarboxylate transporter 8 deficiency: case reports and literature review of cases in Japan[J]. Front Neurol, 2021, 12: 657820.
[17] Sakata Y, Sano K, Aoki S, et al. Neurochemistry evaluated by MR spectroscopy in a patient with SPTAN1-related developmental and epileptic encephalopathy[J]. Brain Dev, 2022, 44(6): 415-420.
[18] Hou PS, hAilín Dó, Vogel T, et al. Transcription and beyond: delineating FOXG1 function in cortical development and disorders[J]. Front Cell Neurosci, 2020, 14: 35.
[19] Lu G, Zhang Y, Xia H, et al. Identification of a de novo mutation of the FOXG1 gene and comprehensive analysis for molecular factors in Chinese FOXG1-related encephalopathies[J]. Front Mol Neurosci, 2022, 15: 1039990.
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