Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family
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Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family Tian Zhang 1,2 & Mingwu Chen 1,2
&
Angang Zhu 3 & Xiaoguang Zhang 1,2 & Tao Fang 1
Received: 21 October 2019 / Accepted: 3 February 2020 # The Author(s) 2020
Abstract Generalized epilepsy with febrile seizures plus (GEFS+) is a complex familial epilepsy syndrome. It is mainly caused by mutations in SCN1A gene, encoding type 1 voltage-gated sodium channel α-subunit (NaV1.1), and GABRA1 gene, encoding the α1 subunit of the γ-aminobutyric acid type A (GABAA) receptor, while seldom related with SCN9A gene, encoding the voltage-gated sodium channel NaV1.7. In this study, we investigated a Chinese family with an autosomal dominant form of GEFS+. DNA sequencing of the whole coding region revealed a novel heterozygous nucleotide substitution (c.5873A>G) causing a missense mutation (p.Y1958C). This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). Our finding reports a novel likely pathogenic SCN9A Y1958C heterozygous mutation in a Chinese family with GEFS+ and provides additional supports that SCN9A variants may be associated with human epilepsies. Keywords SCN9A . Mutation . |Epilepsy . Generalized epilepsy with febrile seizures plus
Introduction SCN9A gene encodes the voltage-gated sodium channel NaV1.7, one of the nine known α members of voltage-gated sodium (Nav) channels [1]. It mainly expresses in dorsal root ganglion neurons, thus its mutations are mainly associated with pain disorders [2]. However, more and more studies have shown that SCN9A mutations in patients are also associated with variable epilepsy phenotypes including febrile seizures (FS) [3], GEFS+ [4], and Dravet syndrome (DS) [5] in recent years. GABRG2 gene (γ-aminobutyric acid receptor subunit
gene), SCN1A gene, and GABRA1 gene are most frequently mentioned in GEFS+ [6–8], while the role of SCN9A gene in GEFS+ still remains unknown. Here, we report a novel previously unreported likely pathogenic SCN9A Y1958C heterozygous mutation with no SCN1A mutations in a Chinese family with GEFS+ and explore the possibility of SCN9A contributing to GEFS+.
Material and methods Family recruitment
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10072-020-04284-x) contains supplementary material, which is available to authorized users. * Mingwu Chen [email protected]
A family with 10 living Han members across three generation participated in the study. All the subjects signed the informed consent. Clinical data were collected from all members.
Targeted exon capture and sequencing 1
Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China
2
Department of Pediatrics, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui, China
3
Department of Pediatrics, A
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