ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature

Clara Houdayer; Kathleen Rooney; Liselot van der Laan; Céline Bris; Mariëlle Alders; Angela Bahr; Giulia Barcia; Clarisse Battault; Anais Begemann; Dominique Bonneau; Antoine Bonnevalle; Aicha Boughalem; Alice Bourges; Marie Bournez; Ange-Line Bruel; Daniela Buhas; Floriane Carallis; Benjamin Cogné; Valérie Cormier-Daire; Julian Delanne; Tanguy Demaret; Anne-Sophie Denommé-Pichon; Julie Désir; Christèle Dubourg; Mélanie Fradin; David Geneviève; Himanshu Goel; Alice Goldenberg; Karen W Gripp; Agnès Guichet; Anne Guimier; Adeline Jacquinet; Boris Keren; Louis Legoff; Michael A Levy; Haley Mcconkey; Bryce A Mendelsohn; Cyril Mignot; Vincent Milon; Mathilde Nizon; Beatrice Oneda; Laurent Pasquier; Olivier Patat; Christophe Philippe; Vincent Procaccio; Rebecca Procopio; Clément Prouteau; Thomas Rambaud; Anita Rauch; Raissa Relator; Sophie Rondeau; Gijs W E Santen; Jennifer Schleit; Arthur Sorlin; Katharina Steindl; Matt Tedder; Marine Tessarech; Frédéric Tran Mau-Them; Detlef Trost; Pleuntje J van der Sluijs; Marie Vincent; Sandra Whalen; Christel Thauvin-Robinet; Bertrand Isidor; Bekim Sadikovic; Antonio Vitobello; Estelle Colin

doi:10.1038/s41431-025-01798-w

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ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature

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ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature

Clara Houdayer, Kathleen Rooney, Liselot van der Laan, Céline Bris, Mariëlle Alders, Angela Bahr, Giulia Barcia, Clarisse Battault, Anais Begemann, Dominique Bonneau, …

European Journal of Human Genetics

05/03/2025

DOI: https://doi.org/10.1038/s41431-025-01798-w

Résumé

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.

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Titre: ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature
Créateurs - sans rôle: Clara Houdayer - Université d'Angers
Kathleen Rooney - Western University
Liselot van der Laan - Amsterdam University Medical Centers
Céline Bris - Inserm
Mariëlle Alders - Amsterdam University Medical Centers
Angela Bahr - University of Zurich
Giulia Barcia - Hôpital Necker-Enfants Malades
Clarisse Battault - Centre Hospitalier Universitaire d'Angers
Anais Begemann - University of Zurich
Dominique Bonneau - Centre Hospitalier Universitaire d'Angers
Antoine Bonnevalle - Université de Rouen Normandie
Aicha Boughalem - Virbac
Alice Bourges - Centre Hospitalier Universitaire d'Angers
Marie Bournez - CHU Dijon Bourgogne
Ange-Line Bruel - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
Daniela Buhas - McGill University
Floriane Carallis - Inovarion
Benjamin Cogné - Centre National de la Recherche Scientifique
Valérie Cormier-Daire - Inserm
Julian Delanne - CHU Dijon Bourgogne
Tanguy Demaret - Institute of Pathology and Genetics
Anne-Sophie Denommé-Pichon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
Julie Désir - Institute of Pathology and Genetics
Christèle Dubourg - Centre Hospitalier Universitaire de Rennes
Mélanie Fradin - Centre Hospitalier Universitaire de Rennes
David Geneviève - Université de Montpellier
Himanshu Goel - Hunter Genetics
Alice Goldenberg - Université de Rouen Normandie
Karen W Gripp - Community Health Systems - Dupont Hospital
Agnès Guichet - Centre Hospitalier Universitaire d'Angers
Anne Guimier - Assistance Publique – Hôpitaux de Paris
Adeline Jacquinet - University of Liège
Boris Keren - Sorbonne Université
Louis Legoff - Centre Hospitalier Universitaire d'Angers
Michael A Levy - London Health Sciences Centre
Haley Mcconkey - London Health Sciences Centre
Bryce A Mendelsohn - Kaiser Permanente Oakland Medical Center
Cyril Mignot - Centre d'Épidémiologie sur les Causes Médicales de Décès
Vincent Milon - Centre Hospitalier Universitaire d'Angers
Mathilde Nizon - Institut du Thorax
Beatrice Oneda - University of Zurich
Laurent Pasquier - Centre Hospitalier Universitaire de Rennes
Olivier Patat - Université de Toulouse
Christophe Philippe - CHU Dijon Bourgogne
Vincent Procaccio - Université d'Angers
Rebecca Procopio - Community Health Systems - Dupont Hospital
Clément Prouteau - Centre Hospitalier Universitaire d'Angers
Thomas Rambaud - Laboratoire de Biologie Médicale SeqOIA [Paris]
Anita Rauch - University of Zurich
Raissa Relator - London Health Sciences Centre
Sophie Rondeau - Hôpital Necker-Enfants Malades
Gijs W E Santen - Leiden University Medical Center
Jennifer Schleit - Quest Diagnostics
Arthur Sorlin - CHU Dijon Bourgogne
Katharina Steindl - University of Zurich
Matt Tedder - Greenwood Genetic Center
Marine Tessarech - Inserm
Frédéric Tran Mau-Them - CHU Dijon Bourgogne
Detlef Trost - Virbac
Pleuntje J van der Sluijs - Leiden University Medical Center
Marie Vincent - Centre National de la Recherche Scientifique
Sandra Whalen - Hôpital Armand-Trousseau
Christel Thauvin-Robinet - CHU Dijon Bourgogne
Bertrand Isidor - Institut du Thorax
Bekim Sadikovic - London Health Sciences Centre
Antonio Vitobello - CHU Dijon Bourgogne
Estelle Colin - Inserm
Détails de publication: European Journal of Human Genetics
Identifiants: 99160539909311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article
Champs locaux: hal-05105877