biostudies-literatureLaue KEuropean Commission FP7595-606https://www.ebi.ac.uk/biostudies/studies/S-EPMC3213388biostudies-literatureUnknown89(5)Excess exogenous retinoic acid (RA) has been well documented to have teratogenic effects in the limb and craniofacial skeleton. Malformations that have been observed in this context include craniosynostosis, a common developmental defect of the skull that occurs in 1 in 2500 individuals and results from premature fusion of the cranial sutures. Despite these observations, a physiological role for RA during suture formation has not been demonstrated. Here, we present evidence that genetically based alterations in RA signaling interfere with human development. We have identified human null and hypomorphic mutations in the gene encoding the RA-degrading enzyme CYP26B1 that lead to skeletal and craniofacial anomalies, including fusions of long bones, calvarial bone hypoplasia, and craniosynostoAmerican journal of human geneticsCraniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid.PMC3213388FP7_242048Kubisch Cvon Ameln SAlanay YHammerschmidt MDaniel PBGray MJRachwalski MBreuning MHSawyer GMNikkels PGLaue KBloch Wvan Haeringen ASutherland-Smith AJWollnik BMorgan TPogoda HMRobertson SPfalseCraniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid.Excess exogenous retinoic acid (RA) has been well documented to have teratogenic effects in the limb and craniofacial skeleton. Malformations that have been observed in this context include craniosynostosis, a common developmental defect of the skull that occurs in 1 in 2500 individuals and results from premature fusion of the cranial sutures. Despite these observations, a physiological role for RA during suture formation has not been demonstrated. Here, we present evidence that genetically based alterations in RA signaling interfere with human development. We have identified human null and hypomorphic mutations in the gene encoding the RA-degrading enzyme CYP26B1 that lead to skeletal and craniofacial anomalies, including fusions of long bones, calvarial bone hypoplasia, and craniosynosto2011-01-01T00:00:00Z2011 Nov2026-05-04T22:26:08.986Z2026-04-07T21:02:30.899ZS-EPMC32133882201927210.1016/j.ajhg.2011.09.015