Truncating Variants in RREB1 Cause a Novel RASopathy Syndrome of Congenital Heart Disease, Genitourinary Malformations, and Developmental Delay.

Fiche publication

Date publication

mai 2025

Journal

American journal of medical genetics. Part A

Auteurs

Membres identifiés du Cancéropôle Est :
Pr PHILIPPE Christophe

Tous les auteurs :
Strong A, McKenna C, Stals K, Vitobello A, Renaud M, Rieubland C, Guipponi M, Philippe C, Vrana P, Gaskell A, Innes AM, Rippert AL, Ahrens-Nicklas R, Bhoj E, Keller K, Chaudhari BP, Stone BS

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40418122

Résumé

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.