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Here we present a cohort of 6 individuals with truncating <jats:italic>RREB1<\/jats:italic> variants. Phenotypes include mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay. Our data support <jats:italic>RREB1<\/jats:italic> as a currently under\u2010recognized cause of a RASopathy phenotype with features that overlap with Noonan, Costello, and Cardiofaciocutaneous syndromes.<\/jats:p>","DOI":"10.1002\/ajmg.a.64119","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T08:59:37Z","timestamp":1748249977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Truncating Variants in <scp><i>RREB1<\/i><\/scp> Cause a Novel <scp>RASopathy<\/scp> Syndrome of Congenital Heart Disease, Genitourinary Malformations, and Developmental Delay"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-244X","authenticated-orcid":false,"given":"Alanna","family":"Strong","sequence":"first","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caoimhe","family":"McKenna","sequence":"additional","affiliation":[{"name":"Northern Ireland Regional Genetics Service, Belfast Health and Social Care Trust  Belfast Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Stals","sequence":"additional","affiliation":[{"name":"Exeter Genomics Laboratory  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3717-8374","authenticated-orcid":false,"given":"Antonio","family":"Vitobello","sequence":"additional","affiliation":[{"name":"CHU Dijon Bourgogne, Service de G\u00e9nomique m\u00e9dicale\u2014Centre NEOMICS, FHU Translad, Dijon, France  Dijon France"},{"name":"Universit\u00e9 Bourgogne Europe\u2014Inserm UMR1231 \u00e9quipe GAD  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Renaud","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique\u2014H\u00f4pital d'enfants\u2014CHRU de Nancy  Nancy France"},{"name":"Service de Neurologie\u2014H\u00f4pital Central\u2014CHRU de Nancy  Nancy France"},{"name":"INSERM U1256 NGERE\u2014Nutrition\u2014G\u00e9n\u00e9tique et Exposition aux Risques Environnementaux\u2014Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Lorraine  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Rieubland","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Diagnostic Department Geneva University Hospitals  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Guipponi","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Diagnostic Department Geneva University Hospitals  Geneva Switzerland"},{"name":"Department of Genetic Medicine and Development, Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Philippe","sequence":"additional","affiliation":[{"name":"CHR Metz Thionville Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital Mercy  Metz France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Vrana","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Precision Diagnostics Laboratory Children's Hospital of Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Gaskell","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Precision Diagnostics Laboratory Children's Hospital of Colorado  Aurora Colorado USA"},{"name":"Precision Medicine Institute Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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