Modulating effects of FGF12 variants on Na_V1.2 and Na_V1.6 being associated with developmental and epileptic encephalopathy and Autism spectrum disorder: A case series.

ABSTRACT:

Objective

Fibroblast Growth Factor 12 (FGF12) may represent an important modulator of neuronal network activity and has been associated with developmental and epileptic encephalopathy (DEE). We sought to identify the underlying pathomechanism of FGF12-related disorders.

Methods

Patients with pathogenic variants in FGF12 were identified through published case reports, GeneMatcher and whole exome sequencing of own case collections. The functional consequences of two missense and two copy number variants (CNVs) were studied by co-expression of wildtype and mutant FGF12 in neuronal-like cells (ND7/23) with the sodium channels Na_V1.2 or Na_V1.6, including their beta-1 and beta-2 sodium channel subunits (SCN1B and SCN2B).

Results

Four variants in FGF12

SUBMITTER: Seiffert S 

PROVIDER: S-EPMC9429545 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature