Influence of common SCN1A promoter variants on the severity of SCN1A-related phenotypes.

ABSTRACT:

Background

Pathogenic variants in SCN1A cause variable epilepsy disorders with different disease severities. We here investigate whether common variation in the promoter region of the unaffected SCN1A allele could reduce normal expression, leading to a decreased residual function of Nav1.1, and therefore to more severe clinical outcomes in patients affected by pathogenic SCN1A variants.

Methods

Five different SCN1A promoter-haplotypes were functionally assessed in SH-SY5Y cells using Firefly and Renilla luciferase assays. The SCN1A promoter region was analyzed in a cohort of 143 participants with SCN1A pathogenic variants. Differences in clinical features and outcomes between participants with and without common variants in the SCN1A promoter-region of their unaffected allel

SUBMITTER: de Lange IM 

PROVIDER: S-EPMC6625088 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature