GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301886/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301886GEOGSEfalseTrisomy 21 drives ADARB1 overexpression and premature RNA recoding in the developing fetal brainUnderstanding how chromosome 21 gene dosage contributes to neurodevelopmental and systemic phenotypes in trisomy 21 (T21) remains a fundamental challenge. We performed transcriptome-wide RNA sequencing on fetal cortical and hippocampal tissues from 20 T21 cases and 27 euploid controls collected between 13–22weeks post-conception—a critical period for human brain development. Differential expression analysis revealed 572 dysregulated genes in the cortex and 519 in the hippocampus (FDR < 5%), with significant enrichment for chromosome 21 genes. Functional enrichment analyses highlighted disruptions in neurodevelopmental, synaptic, and immune-related pathways. Among the most strongly dysregulated genes was ADARB1, a chromosome 21–encoded RNA editing enzyme, whose overexpression in T21 fetal brain was associated with increased adenosine-to-inosine (A-to-I) editing, including key recoding events in GRIA2 (p.R764G), GRIA3 (p.R775G), and GRIK2 (p.Y571C, p.Q621R). A meta-analysis incorporating nine independent transcriptomic datasets spanning early embryonic and progenitor cell types validated robust chromosome 21 dosage effects, including consistent ADARB1 overexpression. Extending these findings, a meta-analysis of A-to-I editing across datasets revealed widespread over-editing at 3′UTRs and at GRIA3 (p.R775G), a site critical for AMPA receptor desensitization. Together, these results implicate dysregulated RNA editing—driven by ADARB1 overexpression—as a novel post-transcriptional mechanism contributing to fetal neuropathology in T21 and provide a framework for understanding the broader molecular consequences of chromosome 21 dosage sensitivity during brain development.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 sapiens[41917044]