Fiche publication
Date publication
novembre 2025
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr NAMBOT Sophie
Tous les auteurs :
Mirzaa GM, Yan K, Relator R, Levesque M, Jayasinghe P, Timpano S, Yalcin B, Collins S, Ziegler A, Pao E, Oyama N, Brischoux-Boucher E, Piard J, Monaghan KG, Guillen Sacoto MJ, Dobyns WB, Park KL, Fernández-Mayoralas DM, Fernández-Jaén A, Jayakar P, Palomares-Bralo M, Santos-Simarro F, Brusco A, Antona V, Giorgio E, Kvarnung M, Isidor B, Conrad S, Cogné B, Deb W, Stuurman KE, Štěrbová K, Smal N, Weckhuysen S, Oegema R, Innes AM, Koboldt DC, Ben-Omran T, Yeh RC, Kruer MC, Bakhtiari S, Papavasiliou A, Moutton S, Nambot S, Chanprasert S, Paolucci SA, Miller K, Burton B, Kim K, O'Heir E, Bruwer Z, Donald KA, Kleefstra T, Goldstein A, Angle B, Bontempo K, Miny P, Joset P, Demurger F, Hobson E, Pang L, Carpenter L, Li D, Bonneau D, Sadikovic B, Picketts DJ
Lien Pubmed
Résumé
Pathogenic variants in ATP-dependent chromatin remodeling proteins are a recurrent cause of neurodevelopmental disorders (NDDs). The NURF complex consists of BPTF and either the SMARCA5 or SMARCA1 ISWI-chromatin remodeling enzyme. Pathogenic variants in BPTF and SMARCA5 have been previously implicated in NDDs. Here, we describe 35 individuals from 26 families with de novo or maternally inherited variants in the X-linked SMARCA1 gene. This SMARCA1-related NDD is associated with a spectrum of involvement, including mild to severe ID/DD, delayed or regressive speech development, ASD features, facial dysmorphisms, and other variable features. Individuals carrying SMARCA1 truncating variants exhibit a mildly unique genome-wide DNA methylation profile and a high penetrance of macrocephaly. Genetic dissection of the NURF complex using Smarca1, Smarca5, and Bptf single and double mouse knockouts reveals the importance of NURF composition and dosage for proper forebrain development. We propose that genetic alterations affecting different NURF components, including SMARCA1, result in a NDD with a broad clinical spectrum.
Référence
Nat Commun. 2025 11 10;16(1):9875
