Whole exome sequencing and co-expression analysis identify an SCN1A variant that modifies pathogenicity in a family with genetic epilepsy and febrile seizures plus.

ABSTRACT:

Objective

Family members carrying the same SCN1A variant often exhibit differences in the clinical severity of epilepsy. This variable expressivity suggests that other factors aside from the primary sodium channel variant influence the clinical manifestation. However, identifying such factors has proven challenging in humans.

Methods

We perform whole exome sequencing (WES) in a large family in which an SCN1A variant (p.K1372E) is segregating that is associated with a broad spectrum of phenotypes ranging from lack of epilepsy, to febrile seizures and absence seizures, to Dravet syndrome. We assessed the hypothesis that the severity of the SCN1A-related phenotype was affected by alternate alleles at a modifier locus (or loci).

Results

One of our top candidates identifie

SUBMITTER: Hammer MF 

PROVIDER: S-EPMC10753192 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature