ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature
Year: 2025
Type: article
Abstract: Rare genetic variants in ARID2 are responsible for a recently described neurodevelopmental condition called ARID2-related disorder (ARID2-RD). ARID2 belongs to PBAF, a unit of the SWI/SNF complex, which is a chromatin remodeling complex. This work aims to further delineate the phenotypic spectrum of ARID2-RD, providing clinicians with additional data for better care and aid in the future diagnosis of this condition. We obtained the genotypes and phenotypes of 27 previously unreported individuals with ARID2-RD and compared this series with findings in the literature. We also assessed peripheral blood DNA methylation profiles in individuals with ARID2-RD compared to episignatures of controls, unresolved cases, and other neurodevelopmental disorders. The main clinical features of ARID2-RD are developmental delay, speech disorders, intellectual disability (ID), behavior problems, short stature, and various dysmorphic and ectodermal features. Genome-wide differential methylation analysis revealed a global hypermethylated profile in ARID2-RD that could aid in reclassifying variants of uncertain significance. Our study doubles the number of reported individuals with ARID2 pathogenic variants to 53. It confirms loss-of-function as a pathomechanism and shows the absence of a clear genotype-phenotype correlation. We provide evidence for a unique DNA methylation episignature for ARID2-RD and further delineate the ARID2-associated phenotype.
DOI: 10.5167/uzh-276243
Authors: Houdayer, Clara, Rooney, Kathleen, van der Laan, Liselot, Bris, Céline, Alders, Mariëlle, Bahr, Angela, Barcia, Giulia, Battault, Clarisse, Begemann, Anais, Bonneau, Dominique, Bonnevalle, Antoine, Boughalem, Aicha, Bourges, Alice, Bournez, Marie, Bruel, Ange-Line, Buhas, Daniela, Carallis, Floriane, Cogné, Benjamin, Cormier-Daire, Valérie, Delanne, Julian, Demaret, Tanguy, Denommé-Pichon, Anne-Sophie, Desir, Julie, Dubourg, Christèle, Fradin, Mélanie, Geneviève, David, Goel, Himanshu, Oneda, Beatrice, Rauch, Anita, Steindl, Katharina, et al
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6929802574
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