SCN1A gain of function effects in Dravet syndrome: Insights into clinical phenotypes and therapeutic implications.

ABSTRACT: A large number of cases with Dravet syndrome (DS) has been attributed to SCN1A loss of function (LOF), whereas SCN1A gain-of-function (GOF) causes early infantile developmental and epileptic encephalopathy (EIDEE) and familial hemiplegic migraine 3. We retrospectively analyzed 37 individuals with SCN1A pathogenic variants at our institute between January 2012 and October 2024 to investigate phenotype-function correlations. Variant functions were classified as LOF, GOF, or mixed, based on existing patch-clamp data, paralog sodium channel experimental findings, and in silico prediction tools. Clinical characteristics, antiseizure medication (ASM) responses, and variant location were compared. Nine variants were novel. One variant with insufficient data for functional prediction was excluded.

SUBMITTER: Kobayashi Takahashi Y 

PROVIDER: S-EPMC12362185 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature