STX1B Variant-Specific Synaptic Dysfunction Drives Network Hyperexcitability in Human iPSC-derived Neurons

Transcriptomic profiling revealed overlapping and variant-specific gene expression changes affecting synaptic signaling, cytoskeletal organization, and vesicle trafficking. Importantly, all human neuronal cultures were co-cultured with mouse astrocytes serving as feeder layers. As a consequence, the corresponding FASTQ files contain a substantial fraction of mouse-derived reads.

These were rigorously filtered out prior to downstream analysis to retain only human reads; however, users accessing or re-analyzing these data should be aware of this mixed human-mouse origin of the raw sequencing files. Together, these data demonstrate that distinct STX1B variants induce convergent network hyperexcitability through differential synaptic and molecular mechanisms, providing mechanistic insight into the pathophysiology of STX1B-related epilepsies.