This is particularly important given that patUPD15 (and imprinting defect) cases of Angelman syndrome were excluded from clinical trials (clinicaltrials.gov, NCT04259281, NCT04428281, NCT06914609, NCT06415344) using modified antisense oligonucleotide (mASO) technology to reinstate UBE3A expression by activating the paternal allele through RNase H-mediated degradation of the UBE3A-ATS. Here, UBE3A is linked to Angelman syndrome.