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Multi-omics profiling reveals convergent MAGEL2-driven defects in human corticogenesis across Prader-Willi and Schaaf-Yang syndromes.

ABSTRACT: To enable advanced cognitive abilities, the human cortex undergoes complex developmental processes, disruption of which underlies neurodevelopmental disorders such as Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). While SYS is caused by pathogenic point mutations in the imprinted MAGEL2 gene, PWS arises from chromosomal deletions, imprinting defects or uniparental disomy encompassing the MAGEL2 locus. Here, bulk RNA-seq was performed on day-30 hiPSC-derived cortical neurons from two CRISPR/Cas9-engineered isogenic human pluripotent stem cell backgrounds (male GM08330 and female MGH2069) modeling MAGEL2-associated SYS and PWS variants, including WT, MAGEL2 c.1996dupC, MAGEL2 c.1996delC, heterozygous MAGEL2 deletion, homozygous MAGEL2 deletion, PWS type I deletion, and PWS type II deletion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE329288 | GEO | 2026/08/21

REPOSITORIES: GEO

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