GABRG1 variant as a potential novel cause of epileptic encephalopathy, hypotonia, and global developmental delay.
GABA-A receptor
GABRG1
epileptic encephalopathies
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
16
08
2022
received:
10
08
2022
accepted:
18
08
2022
pubmed:
20
9
2022
medline:
15
11
2022
entrez:
19
9
2022
Statut:
ppublish
Résumé
Epileptic encephalopathies (EEs) are severe brain disorders with excessive ictal (seizure) and interictal (electrographic epileptiform discharges) activity in developing brain which may result in progressive cognitive and neuropsychological deterioration. In contrast to regular epilepsy where the treatment goal is to prevent the seizure (ictal) recurrence, in patients with EE the goal is to treat both ictal as well as interictal activity to prevent further progression. With the introduction of genetic sequencing technologies over the past 20 years, there is growing recognition of the genetic basis of EE, with the majority due to monogenic causes. Monogenic etiologies of EE include pathogenic variants in the γ-aminobutyric acid type A receptor (GABA-A) encoding gene family. We present a 2-year-old patient with EE, hypotonia, and global developmental delays. Clinical trio exome sequencing showed a novel, de novo variant in GABRG1. GABRG1 encodes the γ1 subunit of the GABA-A receptor. To date, there has not been an association of EE with pathogenic variants in GABRG1. This variant is predicted to be damaging to protein structure and function, and the patient's phenotype is similar to those with pathogenic variants in other members of the GABA-A receptor encoding gene family.
Identifiants
pubmed: 36121006
doi: 10.1002/ajmg.a.62969
doi:
Substances chimiques
Receptors, GABA-A
0
GABRG1 protein, human
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
3546-3549Informations de copyright
© 2022 Wiley Periodicals LLC.
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