The p.L218P variant in WDR83 disrupts neuronal development, leading to neurodevelopmental disorder.

ABSTRACT: WDR83 (WD Repeat Domain 83), also known as MORG1 (Mitogen-activated protein kinase Organizer 1), functions as a scaffold protein regulating diverse cellular processes, including cell signaling, proliferation, protein degradation, cell polarity, and autophagy. Through whole-exome sequencing, we identified a novel de novo WDR83 variant [NM_001099737; c.653 T > C,p.(L218P)] in a Japanese female patient presenting with global developmental delay, intellectual disability, and dysmorphic features. As the p.L218P variant was suspected to exert a dominant-negative effect, we investigated its impact on neuronal development. In vivo, acute expression via in utero electroporation promoted premature cell cycle exit of neural stem cells, impaired cortical neuron migration, and disrupted dendritic arbor

SUBMITTER: Tabata H 

PROVIDER: S-EPMC12816048 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature