Prader-Willi syndrome (PWS) is a neurodevelopmental disorder, characterized by hyperphagia, developmental delay and cognitive deficits. The PWS genomic locus (15q11-q13) is maternally imprinted and the pathology arises when the paternal genome copy is deleted, with maternal uniparental disomy of chromosome 15 or imprinting defects. This genomic locus harbors different C/D box small nucleolar RNAs (SNORDs) that feature short transcripts usually involved in post-transcriptional modifications of rRNA. In particular, SNORD116 is included in the majority of the disease-causing chromosomal deletions. SNORD116 is supposed to lack RNA targets, but instead it might be implicated in noncanonical processes including mRNA regulation and alternative splicing. In this work, we exploited patient-derived induced pluripotent stem cell (iPSC)-derived neuronal cultures with the aim of unraveling the molecular alterations triggered by SNORD116 loss.We have refined a protocol to generate mature cortical excitatory neurons from Prader-Willi patients and unrelated healthy controls. Patient and control neuronal samples were then processed for bulk RNA-seq to identify differently expressed genes (DEGs). Next, DEGs were analyzed with a dedicated software to predict if the altered genes could be direct SNORD116 candidate targets.This cross-reference analysis identified 12 genes, and among them we focused on CHRNA7 that was up-regulated in all patients and a direct candidate target of SNORD116.CHRNA7 encodes for the subunit 7 of the nicotinic acetylcholine receptor (nAcrR7) regulating cognitive and behavioral functions. Studies are in progress to assess protein changes of the nAcrR7 sub-unit. Moreover, electrophysiological studies will confirm if nAcrR7 upregulation can impair excitability of cortical neurons.