ASXL3 truncating patient variants mediate transcriptional gain-of-function and are antisense oligonucleotide-responsive
Yuji Nakamura, Toan Nguyen, Nofar Mor, Dan Dominissini, Isaac Tang, Christopher J. Torio, Harikrishna Thulaseedharan, Rachel Yibei Zhou, Wenshu Zhang, Konstantina Skourti-Stathaki, Julie Douville, Laurence Mignon, Ashley Dung, Susan M. Freier, Andrew T. Watt, , Joseph G. Gleeson
The paper shows ASXL3 truncating variants cause disease via gain-of-function, not loss-of-function, and demonstrates antisense oligonucleotides can reverse the transcriptional effects.
medRxiv · Jul 22, 2026 · PreprintGenetic & Genomic Medicine