Spectrum of K_V 2.1 Dysfunction in KCNB1-Associated Neurodevelopmental Disorders.

ABSTRACT:

Objective

Pathogenic variants in KCNB1, encoding the voltage-gated potassium channel K_V 2.1, are associated with developmental and epileptic encephalopathy (DEE). Previous functional studies on a limited number of KCNB1 variants indicated a range of molecular mechanisms by which variants affect channel function, including loss of voltage sensitivity, loss of ion selectivity, and reduced cell-surface expression.

Methods

We evaluated a series of 17 KCNB1 variants associated with DEE or other neurodevelopmental disorders (NDDs) to rapidly ascertain channel dysfunction using high-throughput functional assays. Specifically, we investigated the biophysical properties and cell-surface expression of variant K_V 2.1 channels expressed in heterologous cells using

SUBMITTER: Kang SK 

PROVIDER: S-EPMC7025436 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature