Understanding the new <scp> <i>BRD4</i> </scp> ‐related syndrome: Clinical and genomic delineation with an international cohort study
Guillaume Jouret, Solveig Heide, Arthur Sorlin, Laurence Faivre, Sandra Chantot‐Bastaraud, Claire Bénéteau, Marie Denis‐Musquer, Peter D. Turnpenny, Charles Coutton, Gaëlle Vieville, Julien Thévenon, Austin Larson, Florence Petit, Elise Boudry, Thomas Smol, Bruno Delobel, Bénédicte Duban‐Bedu, Chiara Fallerini, Francesca Mari, Caterina Lo Rizzo, Alessandra Renieri, Jean‐Hubert Caberg, Anne‐Sophie Denommé‐Pichon, Frédéric Tran Mau‐Them, Isabelle Maystadt, Thomas Courtin, Boris Keren, L. Mouthon, Perrine Charles, Silvestre Cuinat, Bertrand Isidor, Philippe Theis, Christian Müller, Marizela Kulisic, Seval Türkmen, Daniel Stieber, Dominique Bourgeois, Emmanuel Scalais, Barbara Klink
Abstract
BRD4 is part of a multiprotein complex involved in loading the cohesin complex onto DNA, a fundamental process required for cohesin-mediated loop extrusion and formation of Topologically Associating Domains. Pathogenic variations in this complex have been associated with a growing number of syndromes, collectively known as cohesinopathies, the most classic being Cornelia de Lange syndrome. However, no cohort study has been conducted to delineate the clinical and molecular spectrum of BRD4-related disorder. We formed an international collaborative study, and collected 14 new patients, including two fetuses. We performed phenotype and genotype analysis, integrated prenatal findings from fetopathological examinations, phenotypes of pediatric patients and adults. We report the first cohort of patients with BRD4-related disorder and delineate the dysmorphic features at different ages. This work extends the phenotypic spectrum of cohesinopathies and characterize a new clinically relevant and recognizable pattern, distinguishable from the other cohesinopathies.