{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:52:18Z","timestamp":1784717538966,"version":"3.55.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is an ultra-rare neurocristopathy with no known genetic or environmental etiology. Rapid-onset obesity over a 3\u201312 month period with onset between ages 1.5\u20137 years of age is followed by an unfolding constellation of symptoms including severe hypoventilation that can lead to cardiorespiratory arrest in previously healthy children if not identified early and intervention provided. Congenital Central Hypoventilation syndrome (CCHS) and Prader-Willi syndrome (PWS) have overlapping clinical features with ROHHAD and known genetic etiologies. Here we compare patient neurons from three pediatric syndromes (ROHHAD, CCHS, and PWS) and neurotypical control subjects to identify molecular overlap that may explain the clinical similarities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Dental pulp stem cells (DPSC) from neurotypical control, ROHHAD, and CCHS subjects were differentiated into neuronal cultures for RNA sequencing (RNAseq). Differential expression analysis identified transcripts variably regulated in ROHHAD and CCHS vs. neurotypical control neurons. In addition, we used previously published PWS transcript data to compare both groups to PWS patient-derived DPSC neurons. Enrichment analysis was performed on RNAseq data and downstream protein expression analysis was performed using immunoblotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three transcripts differentially regulated in all three syndromes vs. neurotypical control subjects. Gene ontology analysis on the ROHHAD dataset revealed enrichments in several molecular pathways that may contribute to disease pathology. Importantly, we found 58 transcripts differentially expressed in both ROHHAD and CCHS patient neurons vs. control neurons. Finally, we validated transcript level changes in expression of <jats:italic>ADORA2A<\/jats:italic>, a gene encoding for an adenosine receptor, at the protein level in CCHS neurons and found variable, although significant, changes in ROHHAD neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The molecular overlap between CCHS and ROHHAD neurons suggests that the clinical phenotypes in these syndromes likely arise from or affect similar transcriptional pathways. Further, gene ontology analysis identified enrichments in ATPase transmembrane transporters, acetylglucosaminyltransferases, and phagocytic vesicle membrane proteins that may contribute to the ROHHAD phenotype. Finally, our data imply that the rapid-onset obesity seen in both ROHHAD and PWS likely arise from different molecular mechanisms. The data presented here describes important preliminary findings that warrant further validation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2023.1090084","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T20:12:36Z","timestamp":1683749556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Analysis and comparisons of gene expression changes in patient- derived neurons from ROHHAD, CCHS, and PWS"],"prefix":"10.3389","volume":"11","author":[{"given":"A. 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