Loss-of-function variants in the KCNQ5 gene are implicated in genetic generalized epilepsies.

ABSTRACT:

Background

De novo missense variants in KCNQ5, encoding the voltage-gated K⁺ channel K_V7.5, have been described to cause developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms.

Methods

1292 families with GGE were studied by next-generation sequencing. Whole-cell patch-clamp recordings, biotinylation and phospholipid overlay assays were performed in mammalian cells combined with homology modelling.

Findings

We identified three deleterious heterozygous missense variants, one truncation and one splice site alteration in five independent families with GGE with predominant absence seizures; two variants

SUBMITTER: Kruger J 

PROVIDER: S-EPMC9471468 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature