{"doi":"10.1002/ajmg.a.64119","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","abstract":"The interstitial 6p microdeletion syndrome is characterized by dysmorphic facies and structural heart, kidney, brain, and musculoskeletal differences. RREB1 haploinsufficiency and consequent abnormal RAS-MAPK pathway signaling have been proposed as a driver of the disease phenotype; however, apart from a single case report, the phenotype of intragenic RREB1 variants is unknown. Here we present a cohort of 6 individuals with truncating RREB1 variants. Phenotypes include mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay. Our data support RREB1 as a currently under-recognized cause of a RASopathy phenotype with features that overlap with Noonan, Costello, and Cardiofaciocutaneous syndromes.","journal":"American Journal of Medical Genetics Part A","year":2025,"id":532430,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1413588,"name":"Caoimhe McKenna","orcid":"0000-0003-1763-4889","position":1,"is_corresponding":false},{"id":350671,"name":"Karen Stals","orcid":"0000-0002-3255-7044","position":2,"is_corresponding":false},{"id":490079,"name":"Antonio Vitobello","orcid":"0000-0003-3717-8374","position":3,"is_corresponding":false},{"id":1027883,"name":"Mathilde Renaud","orcid":"0000-0002-0061-9378","position":4,"is_corresponding":false},{"id":957304,"name":"Claudine Rieubland","orcid":null,"position":5,"is_corresponding":false},{"id":1219192,"name":"Michel Guipponi","orcid":null,"position":6,"is_corresponding":false},{"id":469183,"name":"Christophe Philippe","orcid":"0000-0001-7098-6520","position":7,"is_corresponding":false},{"id":188054,"name":"Paul B. Vrana","orcid":null,"position":8,"is_corresponding":false},{"id":1413980,"name":"Alisa Gaskell","orcid":null,"position":9,"is_corresponding":false},{"id":242572,"name":"A. Micheil Innes","orcid":"0000-0001-9881-5467","position":10,"is_corresponding":false},{"id":1071438,"name":"Alyssa L. Rippert","orcid":"0000-0003-4735-5223","position":11,"is_corresponding":false},{"id":368519,"name":"Rebecca C. Ahrens‐Nicklas","orcid":"0000-0001-8243-7123","position":12,"is_corresponding":false},{"id":461884,"name":"Elizabeth Bhoj","orcid":"0000-0001-5748-3507","position":13,"is_corresponding":false},{"id":1413981,"name":"Kiersten N Keller","orcid":null,"position":14,"is_corresponding":false},{"id":618985,"name":"Bimal P. Chaudhari","orcid":"0000-0002-0115-949X","position":15,"is_corresponding":false},{"id":1244065,"name":"Brandon S. Stone","orcid":null,"position":16,"is_corresponding":false},{"id":539714,"name":"Alanna Strong","orcid":"0000-0001-9261-244X","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40418122","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}