{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301886/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301886"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Trisomy 21 drives ADARB1 overexpression and premature RNA recoding in the developing fetal brain","description":"Understanding 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.","dates":{"publication":"2026/04/08"},"accession":"GSE301886","cross_references":{"GSM":["GSM9091428","GSM9091429","GSM9091426","GSM9091427","GSM9091424","GSM9091468","GSM9091469","GSM9091425","GSM9091389","GSM9091466","GSM9091422","GSM9091423","GSM9091467","GSM9091420","GSM9091387","GSM9091464","GSM9091421","GSM9091465","GSM9091388","GSM9091462","GSM9091385","GSM9091386","GSM9091463","GSM9091394","GSM9091471","GSM9091472","GSM9091395","GSM9091392","GSM9091470","GSM9091393","GSM9091390","GSM9091391","GSM9091419","GSM9091417","GSM9091418","GSM9091415","GSM9091459","GSM9091416","GSM9091413","GSM9091457","GSM9091458","GSM9091414","GSM9091455","GSM9091411","GSM9091412","GSM9091379","GSM9091456","GSM9091453","GSM9091410","GSM9091454","GSM9091451","GSM9091452","GSM9091383","GSM9091460","GSM9091384","GSM9091461","GSM9091381","GSM9091382","GSM9091380","GSM9091408","GSM9091409","GSM9091406","GSM9091407","GSM9091404","GSM9091448","GSM9091449","GSM9091405","GSM9091446","GSM9091402","GSM9091403","GSM9091447","GSM9091400","GSM9091444","GSM9091401","GSM9091445","GSM9091442","GSM9091443","GSM9091440","GSM9091441","GSM9091450","GSM9091439","GSM9091437","GSM9091438","GSM9091435","GSM9091436","GSM9091433","GSM9091434","GSM9091398","GSM9091431","GSM9091432","GSM9091399","GSM9091396","GSM9091430","GSM9091397"],"GPL":["21290"],"GSE":["301886"],"taxon":["Homo sapiens"],"PMID":["[41917044]"]}}