A mutation in the neonatal isoform of SCN2A causes neonatal-onset epilepsy.
6A
6N
SCN2A
neonatal transcript
switch
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:
03 2022
03 2022
Historique:
revised:
11
10
2021
received:
13
02
2021
accepted:
22
10
2021
pubmed:
8
12
2021
medline:
19
4
2022
entrez:
7
12
2021
Statut:
ppublish
Résumé
SCN2A (sodium channel 2A) encodes the Nav1.2 channel protein in excitatory neurons in the brain. Nav1.2 is a critical voltage-gated sodium channel of the central nervous system. Mutations in SCN2A are responsible for a broad phenotypic spectrum ranging from autism and developmental delay to severe encephalopathy with neonatal or early infantile onset. SCN2A can be spliced into two different isoforms, a neonatal (6N) and an adult (6A) form. After birth, there is an equal or higher amount of the 6N isoform, protecting the brain from the increased neuronal excitability of the infantile brain. During postnatal development, 6N is gradually replaced by 6A. In an infant carrying the novel SCN2A mutation c.643G > A (p.Ala215Thr) only in the neonatal transcript, seizures started immediately after birth. The clinical presentation evolved from a burst-suppression pattern with 30-50 tonic seizures per day to hypsarrhythmia. The first exome analysis, focusing only on common transcripts, missed the diagnosis and delayed early therapy. A reevaluation including all transcripts revealed the SCN2A variant.
Identifiants
pubmed: 34874093
doi: 10.1002/ajmg.a.62581
doi:
Substances chimiques
NAV1.2 Voltage-Gated Sodium Channel
0
Protein Isoforms
0
SCN2A protein, human
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
941-947Informations de copyright
© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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