Fiche publication
Date publication
mars 2025
Journal
European journal of human genetics : EJHG
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence
,
Pr PHILIPPE Christophe
,
Mr DUFFOURD Yannis
,
Pr THAUVIN-ROBINET Christel
Tous les auteurs :
Bruel AL, Vulto-vanSilfhout AT, Bilan F, Le Guyader G, Gilbert-Dussardier B, Le Guillou X, Rondeau S, Rio M, Lee KN, Beil A, Suri M, Guerin F, Ruault V, Goldenberg A, Lecoquierre F, Bertsch N, Anderson R, Yang XR, Inness M, Rikeros-Orozco E, Palomares-Bralo M, Hayek JC, Cech J, Jhuraney A, Kumar RD, Mercimek-Andrews S, Ambrose A, Wakeling EN, Wentzensen IM, Torti E, Gooch C, Faivre L, Philippe C, Duffourd Y, Vitobello A, Thauvin-Robinet C
Lien Pubmed
Résumé
RNA-binding proteins play a key role in post-transcriptional events, such as mRNA splicing, transport, stability, translation and decay. Dysregulation of RNA life can have dramatic consequences. CELF RNA-binding proteins appear to be essential during embryo development. In this study, we identified 15 patients with heterozygous missense or loss-of-function variants in the CELF4 gene by exome or genome sequencing. All variants affecting the N-terminus of the protein are essential and sufficient for the RNA-binding and splicing activity or RRM domains. Most patients presented with neurodevelopmental disorders including global developmental delay/intellectual disability (11/14), seizures (9/15) and overweight/obesity (10/14) that began in childhood. Clinical features are similar to the reported celf4-mouse mutant phenotype. This study highlights the essential role of CELF4 in development and its involvement as a novel etiology of neurodevelopmental disorders with obesity.
Référence
Eur J Hum Genet. 2025 03 19;:
