Identification of potential disease-associated variants in idiopathic generalized epilepsy using targeted sequencing.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
22 Nov 2023
22 Nov 2023
Historique:
received:
31
08
2023
accepted:
07
11
2023
revised:
28
10
2023
medline:
23
11
2023
pubmed:
23
11
2023
entrez:
22
11
2023
Statut:
aheadofprint
Résumé
Many questions remain regarding the genetics of idiopathic generalized epilepsy (IGE), a subset of genetic generalized epilepsy (GGE). We aimed to identify the candidate coding variants of epilepsy panel genes in a cohort of affected individuals, using variant frequency information from a control cohort of the same region. We performed whole-exome sequencing analysis of 121 individuals and 10 affected relatives, focusing on variants of 950 candidate genes associated with epilepsy according to the Genes4Epilepsy curated panel. We identified 168 candidate variants (CVs) in 137 of 950 candidate genes in 88 of 121 affected individuals with IGE, of which 61 were novel variants. Notably, we identified five CVs in known GGE-associated genes (CHD2, GABRA1, RORB, SCN1A, and SCN1B) in five individuals and CVs shared by affected individuals in each of four family cases for other epilepsy candidate genes. The results of this study demonstrate that IGE is a disease with high heterogeneity and provide IGE-associated CVs whose pathogenicity should be proven by future studies, including advanced functional analysis. The low detection rate of CVs in the GGE-associated genes (4.1%) in this study suggests the current incompleteness of the Genes4Epilepsy panel for the diagnosis of IGE in clinical practice.
Identifiants
pubmed: 37993639
doi: 10.1038/s10038-023-01208-3
pii: 10.1038/s10038-023-01208-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.
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