Haploinsufficiency of brain-specific kinase BRSK1 causes epilepsy and neurodevelopmental disorders.

ABSTRACT:

Objective

The BRSK1 gene encodes brain-specific serine/threonine kinase 1 (also known as SAD-B kinase), which is almost exclusively expressed in the brain and plays critical roles in neuronal polarization, neurotransmitter release, mitochondrial dynamics, and neuronal maturation. This study aimed to investigate the pathogenicity of BRSK1 variants in epilepsy and neurodevelopmental disorders.

Methods

Trio-based exome sequencing was performed in 394 probands with epilepsy. Expression analyses and functional validation were conducted using a newly generated Brsk1 exon 4-7 knockout mouse line (Brsk1^Δ4-7), with subsequent behavioral, electrophysiological, proteomic, and phosphoproteomic assessments.

Results

Six novel BRSK1 variants were identified in seven proba

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC12779330 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature