| Title: |
Heterozygous CELF4 variants in the N-term region crucial for the RNA-binding activity, leads to neurodevelopmental disorder and obesity. |
| Authors: |
Bruel, Ange-Line; Silfhout, Anneke Vulto-van; Bilan, Frederic; Guyader, Gwenaël Le; Gilbert-Dussardier, Brigitte; Horn, Xavier Le Guillou; Rondeau, Sophie; RIO, Marlène; Lee, Kristen; Beil, Adelyn; Suri, Mohnish; Guerin, François; Ruault, Valentin; Goldenberg, Alice; Lecoquierre, François; Bertsch, Nicole; Anderson, Rhonda; Yang, Xiao-Ru; Inness, Micheil; Rikeros-Orozco, Emi; Palomares-Bralo, Maria; Hayek, Jennifer; Cech, Jennifer; Jhuraney, Ankita; Kumar, Runjun; Mercimek-Andrews, Saadet; Ambrose, Anastasia; Wakeling, Erin; Wentzensen, Ingrid; Torti, Erin; Gooch, Catherine; Faivre, Laurence; Philippe, Christophe; Duffourd, Yannis; Vitobello, Antonio; Thauvin-Robinet, Christel |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2024 |
| Description: |
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 fifteen 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. |
| Document Type: |
other/unknown material |
| Language: |
unknown |
| DOI: |
10.21203/rs.3.rs-4610126/v1 |
| Availability: |
https://doi.org/10.21203/rs.3.rs-4610126/v1; https://www.researchsquare.com/article/rs-4610126/v1; https://www.researchsquare.com/article/rs-4610126/v1.html |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.BF84AD63 |
| Database: |
BASE |