Network Hypoactivity in ALG13-CDG: Disrupted Developmental Pathways and E/I Imbalance as Early Drivers of Neurological Features in CDG.

ABSTRACT:

Background

ALG13-CDG is an X-linked N-linked glycosylation disorder caused by pathogenic variants in the glycosyltransferase ALG13, leading to severe neurological manifestations. Despite the clear CNS involvement, the impact of ALG13 dysfunction on human brain glycosylation and neurodevelopment remains unknown. We hypothesize that ALG13-CDG causes brain-specific hypoglycosylation that disrupts neurodevelopmental pathways and contributes directly to cortical network dysfunction.

Methods

We generated iPSC-derived human cortical organoids (hCOs) from individuals with ALG13-CDG to define the impact of hypoglycosylation on cortical development and function. Electrophysiological activity was assessed using MEA recordings and integrated with multiomic profiling, including scRNA-seq

SUBMITTER: Shah R 

PROVIDER: S-EPMC12839988 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature