Loss of symmetric cell division of apical neural progenitors drives <i>DENND5A</i>-related developmental and epileptic encephalopathy.

ABSTRACT: Developmental and epileptic encephalopathies (DEEs) are a heterogenous group of epilepsies in which altered brain development leads to developmental delay and seizures, with the epileptic activity further negatively impacting neurodevelopment. Identifying the underlying cause of DEEs is essential for progress toward precision therapies. Here we describe a group of individuals with biallelic variants in DENND5A and determine that variant type is correlated with disease severity. We demonstrate that DENND5A interacts with MUPP1 and PALS1, components of the Crumbs apical polarity complex, which is required for both neural progenitor cell identity and the ability of these stem cells to divide symmetrically. Induced pluripotent stem cells lacking DENND5A fail to undergo symmetric

SUBMITTER: Banks E 

PROVIDER: S-EPMC10863025 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature