CELSR3 variants are associated with febrile seizures and epilepsy with antecedent febrile seizures.
CELSR3
epilepsy
febrile seizures
pathogenic gene
trio-based whole-exome sequencing
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
27
09
2021
received:
18
08
2021
accepted:
27
11
2021
pubmed:
25
12
2021
medline:
29
4
2022
entrez:
24
12
2021
Statut:
ppublish
Résumé
To identify novel pathogenic gene of febrile seizures (FS)/epilepsy with antecedent FS (EFS+). 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. 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. CELSR3 variants are potentially associated with FS/EFS+.
Identifiants
pubmed: 34951123
doi: 10.1111/cns.13781
pmc: PMC8841303
doi:
Substances chimiques
Cadherins
0
Celsr3 protein, human
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
382-389Informations de copyright
© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.
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