De novo heterozygous variants of the RSF1 gene are responsible for a syndromic neurodevelopmental disorder
Year: 2026
Type: article
Abstract: Neurodevelopmental disorders (NDD) are a wide and heterogenous group of conditions due to impaired brain development, orchestrated by the crosstalk between genome and environment. Dynamic chromatin regulation during cortical development is fundamental, and chromatin remodelers are critical determinants of this process. Recently, numerous chromatin remodeling genes have been implicated in NDDs. By altering genes' epigenetic state, mutated chromatin remodelers disrupt the spatiotemporal regulation of gene expression during development, potentially leading to severe consequences. The Remodeling and Spacing Factor 1 (RSF1) gene encodes a ubiquitous nuclear protein involved in chromatin remodeling, crucial for processes such as DNA transcription, replication, and repair. In this study, we identified by gene matching (n = 7) and literature search (n = 4) eleven unrelated individuals harboring de novo or inherited from a symptomatic parent heterozygous variants in RSF1. All individuals had an NDD, whether intellectual disability, autism spectrum disorder or developmental delay. From the seven individuals with detailed clinical information, unspecific and inconsistent associated features were described, including cranio-facial morphological features, musculoskeletal, digestive, vision, tone, epilepsy and brain MRI anomalies. Our data support the hypothesis that RSF1 is important for brain development and a novel candidate gene for syndromic NDDs.
Authors: Céline Jost, Tiffany Busa, Daniel Wegner, Marwan Shinawi, Elise Schaefer, Amélie Piton, Caroline Schluth-Bolard, Perrine Charles, Boris Keren, Katharina Mayerhanser, Theresa Brunet, Ulrich Schatz, Jennifer E. Neil, Christopher A. Walsh, Kathleen Sisco, Alexander J. Paul, Undiagnosed Diseases Network, Chung Lee, Natalie Dykzeul, Devon Bonner, Jonathan A. Bernstein, Erin Sutcliffe, Ingrid M. Wentzensen, Catherine Froehlich, Kaleigh Liebler, Patricia Galvin Parton, Jody Weiss-Burns, Chloé Sagnol, Julian Delanne, Caroline Racine, Christel Thauvin-Robinet, Hana Safraou, Frédéric Tran Mau-Them, Yannis Duffourd, Ange-Line Bruel, Laurence Faivre
Institutions: CHU Dijon Bourgogne, Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Washington University in St. Louis, Hôpitaux Universitaires de Strasbourg, Inserm, Laboratoire de Génétique Médicale, Université de Strasbourg, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, TUM Klinikum, Institut für Humangenetik, Technical University of Munich, Boston Children's Hospital, Howard Hughes Medical Institute, Harvard University, Stanford University, Stony Brook Medicine, Université de Bourgogne, Centre de recherche Translationnelle en Médecine moléculaire
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,790
OpenAlex ID: W7125984579