GABRG2及SCN1A双基因变异致遗传性癫痫伴热性惊厥附加症1例及其家系基因型-表型研究

doi:10.12372/jcp.2026.25e0398

临床儿科杂志 ›› 2026, Vol. 44 ›› Issue (1): 51-55.doi: 10.12372/jcp.2026.25e0398

GABRG2及SCN1A双基因变异致遗传性癫痫伴热性惊厥附加症1例及其家系基因型-表型研究

李跃林¹^,², 李仁可¹^,², 熊玉蓉¹^,², 潘书静¹^,², 张佳丽¹^,², 雷文婷¹^,², 石永媛¹^,², 杨丽娟¹^,², 周朝彬³, 田茂强¹^,²^,³()

1.遵义医科大学附属医院小儿内科（贵州遵义 563003）
2.贵州省儿童医院（贵州遵义 563003）
3.关岭布依族苗族自治县人民医院儿科（贵州安顺 561300）

收稿日期:2025-04-16 录用日期:2025-09-22 出版日期:2026-01-15 发布日期:2026-01-05
通讯作者: 田茂强电子信箱：drmaoqiang@126.com

A case of genetic epilepsy with febrile seizures plus caused by dual variations in GABRG2 and SCN1A and a genotype-phenotype study of the family

LI Yuelin¹^,², LI Renke¹^,², XIONG Yurong¹^,², PAN Shujing¹^,², ZHANG Jiali¹^,², LEI Wenting¹^,², SHI Yongyuan¹^,², YANG Lijuan¹^,², ZHOU Chaobin³, TIAN Maoqiang¹^,²^,³()

1. Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou, China
2. Guizhou Provincial Children’s Hospital, Zunyi 563003, Guizhou, China
3. Department of Pediatrics, Guanling Buyi and Miao Autonomous County People’s Hospital, Anshun 561300, Guizhou, China

Received:2025-04-16 Accepted:2025-09-22 Published:2026-01-15 Online:2026-01-05

摘要/Abstract

摘要：

目的探讨GABRG2及SCN1A双基因变异对遗传性癫痫伴热性惊厥附加症（GEFS+）表型的影响。方法收集1例因“反复抽搐”于2023年5月就诊于儿内科的3岁女童及其三代家系成员的临床资料，通过全外显子组测序（WES）及Sanger测序验证该家系基因变异，结合文献分析基因型-表型关联。结果该家系6例成员中，3例SCN1A（c.5621G>A）突变患者表现为热性惊厥（FS）或晚发药物反应性癫痫；2例GABRG2（c.373C>T）突变患者表现为FS或外显不全；GABRG2及SCN1A双变异的先证者表现为早发耐药性癫痫及惊厥持续状态。文献已报道携带上述单位点突变的2例患者也表现为FS。蛋白质相互作用分析显示，SCN1A与GABRG2可能通过共表达协同调控神经元兴奋性。结论 SCN1A与GABRG2双基因变异可能通过基因修饰效应和功能叠加而加重癫痫表型，提示当临床家系表型差异大时，需警惕基因双变异的功能叠加及修饰效应，及时基因检测有助于精准诊疗及遗传咨询。

关键词: GEFS+, 基因型-表型关联, GABRG2基因, SCN1A基因, 双基因变异

Abstract:

Objective To investigate the phenotypic impact of dual variations in GABRG2 and SCN1A on genetic epilepsy with febrile seizures plus (GEFS+). Methods The clinical data of a 3-year-old girl and her three generations of family members who visited the Pediatric Internal Medicine Department due to "repeated convulsions" in May 2023 were collected. The genetic variations of this family were verified by whole exome sequencing (WES) and Sanger sequencing, and the genotype-phenotypic association was analyzed in combination with the literature. Results Among the 6 members of this family, 3 patients with SCN1A (c.5621G>A) mutations presented with febrile seizures (FS) or late-onset antiseizure medication-responsive epilepsy. Two individuals with isolated GABRG2 mutations presented with FS or incomplete penetrance. The proband, carrying dual mutations, manifested early-onset refractory epilepsy and status epilepticus. Two patients with the same single variant reported in the literature also showed FS. Protein interaction analysis revealed co-expression and functional synergy between SCN1A and GABRG2 in regulating neuronal excitability. Conclusions Dual mutations in SCN1A and GABRG2 may exacerbate epilepsy phenotypes through additive functional effects and genetic modifying mechanisms. Clinicians should be vigilant for synergistic interactions of dual variations in families with heterogeneous phenotypes, and timely genetic testing is critical to guide precision therapy and genetic counseling.

Key words: GEFS+, genotype-phenotype correlation, GABRG2 gene, SCN1A gene, dual gene variations

中图分类号:

李跃林, 李仁可, 熊玉蓉, 潘书静, 张佳丽, 雷文婷, 石永媛, 杨丽娟, 周朝彬, 田茂强. GABRG2及SCN1A双基因变异致遗传性癫痫伴热性惊厥附加症1例及其家系基因型-表型研究[J]. 临床儿科杂志, 2026, 44(1): 51-55.

LI Yuelin, LI Renke, XIONG Yurong, PAN Shujing, ZHANG Jiali, LEI Wenting, SHI Yongyuan, YANG Lijuan, ZHOU Chaobin, TIAN Maoqiang. A case of genetic epilepsy with febrile seizures plus caused by dual variations in GABRG2 and SCN1A and a genotype-phenotype study of the family[J]. Journal of Clinical Pediatrics, 2026, 44(1): 51-55.

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参考文献 19

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项目	患者	性别	携带基因	突变位点	人群频率(gnomAD v4.1)	起病年龄
本研究	例1，母亲	女	SCN1A	p.R1874Q	1.239×10^-6	1岁
	例2，姐姐	女	SCN1A	p.R1874Q	1.239×10^-6	1岁
	例3，外公	男	SCN1A	p.R1874Q	1.239×10^-6	50岁
	例4，父亲	男	GABRG2	p.R125C	1.239×10^-6	－
	例5，弟弟	男	GABRG2	p.R125C	1.239×10^-6	6个月
	例6，先证者	女	SCN1A，GABRG2	p.R1874Q，p.R125C	-	3个月
文献报道	例7^[10]，文献病例	女	GABRG2	p.R125C	1.239×10^-6	2岁1个月
文献报道	例8^[11]，文献病例	男	SCN1A	p.R1874Q	1.239×10^-6	13个月
项目	患者	发作消失年龄	起病症状	抗癫痫药物	诊断	预后（末次随访年龄）
本研究	例1，母亲	2岁	发热、惊厥	无	FS	完全恢复（30岁）
	例2，姐姐	1岁6个月	发热、惊厥	无	FS	完全恢复（7岁）
	例3，外公	55岁	惊厥持续状态、意识障碍	VPA	EP	控制良好（60岁）
	例4，父亲	－	－	－	－	－
	例5，弟弟	7个月	发热、惊厥	无	FS	完全恢复（5岁）
	例6，先证者	未控制	发热、惊厥、惊厥持续状态	VPA、CLB、LEV	CFS→Epi	发作明显减少（5岁）
文献报道	例7^[10]，文献病例	5岁11个月	发热、惊厥	VPA	FS+	控制良好（8岁）
文献报道	例8^[11]，文献病例	NA	发热、惊厥	NA	FS	AESD后轻度智力障碍（NA）

GABRG2及SCN1A双基因变异致遗传性癫痫伴热性惊厥附加症1例及其家系基因型-表型研究

A case of genetic epilepsy with febrile seizures plus caused by dual variations in GABRG2 and SCN1A and a genotype-phenotype study of the family

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