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Genotypic and phenotypic characteristics of sodium channel—associated epilepsy in Chinese population

Journal of Human Genetics (2024)Cite this article

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Abstract

Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein’s pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

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Data availability

The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2021) in National Genomics Data Center (Nucleic Acids Res 2022), China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (GSA-Human: HRA004273) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human.

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Acknowledgements

We thank the subjects and their families for their participation and contribution to the work.

Funding

This work was supported by the National Natural Science Foundation of China (81671362 & 32000075), the financial funding from Department of Science and Technology of Shandong Province (ZR2020QC066 & ZR2020QH102), the financial funding from Jinan Science and Technology Bureau (201907007).

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Authors and Affiliations

  1. Pediatric Research Institute, Children’s Hospital Affiliated to Shandong University (Jinan Children’s Hospital), Jinan, China

    Rui Dong, Haiyan Zhang, Min Xue, Yue Li, Kaihui Zhang, Yuqiang Lv, Yi Liu & Zhongtao Gai

  2. Shandong Provincial Clinical Research Center for Children’s Health and Disease, Jinan, China

    Rui Dong, Ruifeng Jin, Hongwei Zhang, Haiyan Zhang, Min Xue, Yue Li, Kaihui Zhang, Yuqiang Lv, Xiaoying Li, Yi Liu & Zhongtao Gai

  3. Department of neurology, Children’s Hospital Affiliated to Shandong University (Jinan Children’s Hospital), Jinan, China

    Ruifeng Jin & Hongwei Zhang

  4. Neonatology department, Children’s Hospital Affiliated to Shandong University (Jinan Children’s Hospital), Jinan, China

    Xiaoying Li

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Contributions

XL, ZG and YL conceived and designed this study. Experiments were conducted by RD, HZ, KZ, and YL. Data were analyzed by RD, MX, and YL. Clinical diagnosis of the subjects was undertaken by RJ and HZ. The paper was written by RD and YL.

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Correspondence to Xiaoying Li or Yi Liu.

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Dong, R., Jin, R., Zhang, H. et al. Genotypic and phenotypic characteristics of sodium channel—associated epilepsy in Chinese population. J Hum Genet (2024). https://doi.org/10.1038/s10038-024-01257-2

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