Open AccessCELSR3 variants are associated with febrile seizures and epilepsy with antecedent febrile seizures
Author(s) -
Li Jia,
Lin SiMei,
Qiao JingDa,
Liu XiaoRong,
Wang Jie,
Jiang Mi,
Zhang Jing,
Zhong Min,
Chen XuQin,
Zhu Jing,
He Na,
Su Tao,
Shi YiWu,
Yi YongHong,
Liao WeiPing
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13781
Subject(s) - epilepsy , febrile seizure , exome sequencing , missense mutation , in silico , medicine , cohort , gene , genetics , pediatrics , biology , psychiatry , mutation
Aims To identify novel pathogenic gene of febrile seizures (FS)/epilepsy with antecedent FS (EFS+). Methods The trio‐based whole‐exome sequencing was performed in a cohort of 462 cases with FS/EFS+. Silico programs, sequence alignment, and protein modeling were used to predict the damaging of variants. Statistical testing was performed to analyze gene‐based burden of variants. Results Five heterozygous missense variants in CELSR3 were detected in five cases (families) with eight individuals (five females, three males) affected. Two variants were de novo, and three were identified in families with more than one individual affected. All the variants were predicted to be damaging in silico tools. Protein modeling showed that the variants resulted in disappearance of multiple hydrogen bonds and one disulfide bond, which potentially caused functional impairments of protein. The frequency of CELSR3 variants identified in this study was significantly higher than that in controls. All affected individuals were diagnosed with FS/EFS+, including six patients with FS and two patients with EFS+. All cases presented favorable outcomes without neurodevelopmental disorders. Conclusions CELSR3 variants are potentially associated with FS/EFS+.