De novo CLPTM1 variants with reduced GABA
channelopathy
epilepsy
loss-of-function
translational study
trio-based whole-exome sequencing
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
07
08
2023
received:
08
02
2023
accepted:
10
08
2023
medline:
7
11
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
ppublish
Résumé
To investigate the clinical features and potential pathogenesis mechanism of de novo CLPTM1 variants associated with epilepsy. Identify de novo genetic variants associated with epilepsy by reanalyzing trio-based whole-exome sequencing data. We analyzed the clinical characteristics of patients with these variants and performed functional in vitro studies in cells expressing mutant complementary DNA for these variants using whole-cell voltage-clamp current recordings and outside-out patch-clamp recordings from transiently transfected human embryonic kidney (HEK) cells. Two de novo missense variants related to epilepsy were identified in the CLPTM1 gene. Functional studies indicated that CLPTM1-p.R454H and CLPTM1-p.R568Q variants reduced the γ-aminobutyric acid A receptor (GABA This is the first report of functionally relevant variants within the CLPTM1 gene. Patch-clamp recordings showed that these de novo CLPTM1 variants reduce GABA
Substances chimiques
Receptors, GABA-A
0
gamma-Aminobutyric Acid
56-12-2
CLPTM1 protein, human
0
Membrane Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2968-2981Subventions
Organisme : NINDS NIH HHS
ID : NS111619
Pays : United States
Informations de copyright
© 2023 International League Against Epilepsy.
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