SCN1A-related epilepsy with recessive inheritance: Two further families.
Dravet syndrome
Febrile seizures
GEFS+
Recessive inheritance
SCN1A
Journal
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
ISSN: 1532-2130
Titre abrégé: Eur J Paediatr Neurol
Pays: England
ID NLM: 9715169
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
02
12
2020
revised:
29
04
2021
accepted:
31
05
2021
pubmed:
27
6
2021
medline:
13
10
2021
entrez:
26
6
2021
Statut:
ppublish
Résumé
Variants in SCN1A gene, encoding the voltage-gated sodium channel Na We report two novel homozygous SCN1A missense variants in two patients from related parents. Both patients had fever-sensitive epilepsy beginning in the first months of life, followed by afebrile seizures, without severe cognitive impairment. Parents were asymptomatic. Next generation sequencing excluded a pathogenic variant in other genes involved in DEE. Estimation of pathogenicity scores by in-silico tools suggests that the impact of these SCN1A variants is less damaging than that of dominant pathogenic variants. This study provides additional evidence that homozygous variants in SCN1A can cause GEFS+. This recessive inheritance would imply that hypomorphic variants may not necessarily cause epilepsy at the heterozygous state but may decrease the seizure threshold when combined.
Sections du résumé
BACKGROUND
BACKGROUND
Variants in SCN1A gene, encoding the voltage-gated sodium channel Na
METHODS AND RESULTS
RESULTS
We report two novel homozygous SCN1A missense variants in two patients from related parents. Both patients had fever-sensitive epilepsy beginning in the first months of life, followed by afebrile seizures, without severe cognitive impairment. Parents were asymptomatic. Next generation sequencing excluded a pathogenic variant in other genes involved in DEE. Estimation of pathogenicity scores by in-silico tools suggests that the impact of these SCN1A variants is less damaging than that of dominant pathogenic variants.
CONCLUSION
CONCLUSIONS
This study provides additional evidence that homozygous variants in SCN1A can cause GEFS+. This recessive inheritance would imply that hypomorphic variants may not necessarily cause epilepsy at the heterozygous state but may decrease the seizure threshold when combined.
Identifiants
pubmed: 34174751
pii: S1090-3798(21)00122-7
doi: 10.1016/j.ejpn.2021.05.018
pii:
doi:
Substances chimiques
NAV1.1 Voltage-Gated Sodium Channel
0
SCN1A protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
121-124Informations de copyright
Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest None.