ZFHX3变体可导致儿童部分性癫痫和婴儿痉挛症,且结果良好。

IF 3.5 2区 医学 Q2 GENETICS & HEREDITY Journal of Medical Genetics Pub Date : 2024-06-20 DOI:10.1136/jmg-2023-109725
Ming-Feng He, Li-Hong Liu, Sheng Luo, Juan Wang, Jia-Jun Guo, Peng-Yu Wang, Qiong-Xiang Zhai, Su-Li He, Dong-Fang Zou, Xiao-Rong Liu, Bing-Mei Li, Hai-Yan Ma, Jing-Da Qiao, Peng Zhou, Na He, Yong-Hong Yi, Wei-Ping Liao
{"title":"ZFHX3变体可导致儿童部分性癫痫和婴儿痉挛症,且结果良好。","authors":"Ming-Feng He, Li-Hong Liu, Sheng Luo, Juan Wang, Jia-Jun Guo, Peng-Yu Wang, Qiong-Xiang Zhai, Su-Li He, Dong-Fang Zou, Xiao-Rong Liu, Bing-Mei Li, Hai-Yan Ma, Jing-Da Qiao, Peng Zhou, Na He, Yong-Hong Yi, Wei-Ping Liao","doi":"10.1136/jmg-2023-109725","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The <i>ZFHX3</i> gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between <i>ZFHX3</i> variants and epilepsy.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A <i>Drosophila Zfh2</i> knockdown model was used to validate the association between <i>ZFHX3</i> and epilepsy.</p><p><strong>Results: </strong>Compound heterozygous <i>ZFHX3</i> variants were identified in eight unrelated cases. The burden of <i>ZFHX3</i> variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In <i>Zfh2</i> knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The <i>Zfh2</i> knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that <i>ZFHX3</i> orthologous were highly expressed in the embryonic stage and decreased dramatically after birth.</p><p><strong>Conclusion: </strong><i>ZFHX3</i> is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"652-660"},"PeriodicalIF":3.5000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228202/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>ZFHX3</i> variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.\",\"authors\":\"Ming-Feng He, Li-Hong Liu, Sheng Luo, Juan Wang, Jia-Jun Guo, Peng-Yu Wang, Qiong-Xiang Zhai, Su-Li He, Dong-Fang Zou, Xiao-Rong Liu, Bing-Mei Li, Hai-Yan Ma, Jing-Da Qiao, Peng Zhou, Na He, Yong-Hong Yi, Wei-Ping Liao\",\"doi\":\"10.1136/jmg-2023-109725\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The <i>ZFHX3</i> gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between <i>ZFHX3</i> variants and epilepsy.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A <i>Drosophila Zfh2</i> knockdown model was used to validate the association between <i>ZFHX3</i> and epilepsy.</p><p><strong>Results: </strong>Compound heterozygous <i>ZFHX3</i> variants were identified in eight unrelated cases. The burden of <i>ZFHX3</i> variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In <i>Zfh2</i> knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The <i>Zfh2</i> knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that <i>ZFHX3</i> orthologous were highly expressed in the embryonic stage and decreased dramatically after birth.</p><p><strong>Conclusion: </strong><i>ZFHX3</i> is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.</p>\",\"PeriodicalId\":16237,\"journal\":{\"name\":\"Journal of Medical Genetics\",\"volume\":\" \",\"pages\":\"652-660\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228202/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medical Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jmg-2023-109725\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jmg-2023-109725","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

背景:ZFHX3基因在胚胎发育、细胞增殖、神经元分化和神经元死亡中发挥着重要作用。本研究旨在探讨 ZFHX3 基因变异与癫痫之间的关系:方法:对378名部分性(局灶性)癫痫患者进行了全外显子组测序。采用果蝇 Zfh2 基因敲除模型验证 ZFHX3 与癫痫的关系:结果:在8例无关病例中发现了ZFHX3复合杂合变体。多重/特异性统计分析显示,病例队列中 ZFHX3 变体的负担明显较高。在 Zfh2 基因敲除的苍蝇中,癫痫样行为的发生率和持续时间明显高于对照组。Zfh2基因敲除的苍蝇表现出更多的兴奋性神经元点燃。所有患者都出现了部分性癫痫发作。C端/N端变异的五名患者表现为轻度部分性癫痫。另外三名患者中,一名经常出现非惊厥性癫痫状态,两名出现早期痉挛。这三名患者也有神经发育异常,被诊断为发育性癫痫性脑病(DEE),但在接受抗癫痫药物治疗而不使用促肾上腺皮质激素/类固醇后,癫痫不再发作。对时间表达(遗传依赖阶段)的分析表明,ZFHX3同源物在胚胎期高度表达,出生后则急剧下降:结论:ZFHX3 是儿童部分性癫痫和 DEE 的新型致病基因。结论:ZFHX3 是儿童部分性癫痫和 DEE 的新致病基因,婴儿痉挛症患者在不使用促肾上腺皮质激素/类固醇治疗后癫痫不再发作,这意味着基因诊断在精确治疗中具有重要意义。遗传依赖阶段让人们了解了疾病演变过程的内在机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.

Background: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy.

Methods: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy.

Results: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth.

Conclusion: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
期刊最新文献
Rare disease genomic testing in the UK and Ireland: promoting timely and equitable access. Classification of PTEN germline non-truncating variants: a new approach to interpretation. Canadian College of Medical Geneticists: clinical practice advisory document - responsibility to recontact for reinterpretation of clinical genetic testing. UBTF haploinsufficiency associated with UBTF-related global developmental delay and distinctive facial features without neuroregression. K acetyltransferase 2B (KAT2B) variants can be responsible for early onset steroid-resistant nephrotic syndrome.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1