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

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells.

Loss of symmetric cell division of apical neural progenitors drives -related developmental and epileptic encephalopathy.

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 and determine that variant type is correlated with disease severity.

Becker muscular dystrophy caused by an intronic mutation reducing the efficiency of the splice donor site of intron 26 of the dystrophin gene.

We describe an 11-year-old boy with dystrophinopathy who presented with a history of progressive proximal muscle weakness and elevated serum creatine kinase levels at age 6. Sequence analysis of the dystrophin (DMD) gene did not identify a mutation in the coding regions but revealed a nucleotide substitution in intron 26 (c.3603+3A>T).