Defining transcriptome signature consistent between cell types in blood and brain and related to the severity of Prader-Willi syndrome.

This study defined genetic subtype and cell type-specific gene expression changes and dysregulated pathways in the prefrontal cortex (PFC) of individuals with Prader-Willi syndrome (PWS). Genes identified to be differentially expressed consistently between all cell types of the PFC, were examined in blood with their mRNA levels related to the severity of PWS including intellectual functioning and behavioral problems. It was hypothesised that genes identified to be consistently differentially expressed across all cell types in the brain tissues examined from individuals with Prader-Willi syndrome (PWS) would be also affected in blood and with their mRNA levels related to the severity of PWS. Overall design: single-nucleus RNA-sequencing was performed on the PFC tissue from 8 donors with PWS (4 15q11-q13 deletion and 4 non-deletion subtypes) and 4 age and sex-matched neurotypical controls. The shortlisted differentially expressed genes (DEGs) that were shared across all cell types of the brain, were examined using droplet digital PCR (ddPCR) in peripheral blood mononuclear cells (PBMCs) from an independent cohort of 36 individuals with PWS (16 deletion and 20 non-deletion).