An SCN1A gene missense variant in a Chinese Tujia ethnic family with genetic epilepsy with febrile seizures plus

Ling Li; Lamei Yuan; Wen Zheng; Yan Yang; Xiong Deng; Zhi Song; Hao Deng

doi:10.3389/fneur.2023.1229569

An SCN1A gene missense variant in a Chinese Tujia ethnic family with genetic epilepsy with febrile seizures plus

Front Neurol. 2023 Jul 27:14:1229569. doi: 10.3389/fneur.2023.1229569. eCollection 2023.

Authors

Ling Li^#^{1

2}, Lamei Yuan^#^{1

2

3

4}, Wen Zheng³, Yan Yang³, Xiong Deng², Zhi Song³, Hao Deng^{1

2

3

4}

Affiliations

¹ Health Management Center, The Third Xiangya Hospital, Central South University, Changsha, China.
² Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
³ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
⁴ Disease Genome Research Center, Central South University, Changsha, China.

^# Contributed equally.

Abstract

Genetic epilepsy with febrile seizures plus (GEFSP) is a familial epileptic syndrome that is genetically heterogeneous and inherited in an autosomal dominant form in most cases. To date, at least seven genes have been reported to associate with GEFSP. This study aimed to identify the disease-causing variant in a Chinese Tujia ethnic family with GEFSP by using whole exome sequencing, Sanger sequencing, and in silico prediction. A heterozygous missense variant c.5725A>G (p.T1909A) was identified in the sodium voltage-gated channel alpha subunit 1 gene (SCN1A) coding region. The variant co-segregated with the GEFSP phenotype in this family, and it was predicted as disease-causing by multiple in silico programs, which was proposed as the genetic cause of GEFSP, further genetically diagnosed as GEFSP2. These findings expand the genetic and phenotypic spectrum of GEFSP and should contribute to genetic diagnoses, personalized therapies, and prognoses.

Keywords: SCN1A; genetic diagnoses; genetic epilepsy with febrile seizures plus; missense variant; whole exome sequencing.

Grants and funding

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81800219 and 81873686), the Natural Science Foundation of Hunan Province (Grant Nos. 2020JJ3057, 2020JJ4830, and 2020JJ4865), the Province-level College Students' Innovative Training Plan Program (Grant No. S2021105331043), the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (Grant No. YX202109), and the Distinguished Professor of the Lotus Scholars Award Program of Hunan Province, China.