BRD4; BRD4-related syndrome; Cornelia de Lange syndrome; NIPBL; cohesinopathy; BRD4 protein, human; Cell Cycle Proteins; Nuclear Proteins; Transcription Factors; Cell Cycle Proteins/genetics; Child; Female; Genomics; Humans; Mutation; Phenotype; Pregnancy; Transcription Factors/genetics; De Lange Syndrome/diagnosis; De Lange Syndrome/genetics; De Lange Syndrome/pathology; Nuclear Proteins/genetics; De Lange Syndrome; Genetics; Genetics (clinical)
Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Jouret, Guillaume; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
Heide, Solveig; Service de Génétique Cytogénétique, Embryologie Hôpital Pitié-Salpétrière, France
Sorlin, Arthur; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg ; Centre de Génétique, CHU de Dijon, Dijon, France ; Génétique des Anomalies du Développement, Inserm 1231 GAD, Université de Bourgogne, France
Faivre, Laurence; Centre de Génétique, CHU de Dijon, Dijon, France ; Génétique des Anomalies du Développement, Inserm 1231 GAD, Université de Bourgogne, France
Chantot-Bastaraud, Sandra; Service de Génétique Et Embryologie Médicales, CHU Paris Est, Hôpital d'Enfants Armand-Trousseau, France
Beneteau, Claire; Service de Génétique Médicale, CHU de Nantes, Institut de Biologie, France
Denis-Musquer, Marie; Service d'Anatomie et Cytologie Pathologiques, Hôpital-Dieu, Nantes, France
Turnpenny, Peter D; Clinical Genetics Department, Royal Devon and Exeter Hospital, UK
Coutton, Charles ; Service de Génétique Médicale, Grenoble, France
Vieville, Gaëlle; Service de Génétique Médicale, Grenoble, France
Thevenon, Julien; Service de Génétique Médicale, Grenoble, France
Petit, Florence ; Clinique de Génétique "Guy Fontaine", CHU de Lille, France
Boudry, Elise; Institut de Génétique Médicale, CHU de Lille, France
Smol, Thomas; Institut de Génétique Médicale, CHU de Lille, France
Delobel, Bruno; Centre de Génétique Chromosomique, GH de l'Institut, Catholique de Lille, France
Duban-Bedu, Bénédicte; Centre de Génétique Chromosomique, GH de l'Institut, Catholique de Lille, France
Fallerini, Chiara; Medical Genetics Department, University of Siena, Siena, Italy
Mari, Francesca; Medical Genetics Department, University of Siena, Siena, Italy ; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy ; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Renieri, Alessandra; Medical Genetics Department, University of Siena, Siena, Italy ; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
CABERG, Jean-Hubert ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Denommé-Pichon, Anne-Sophie ; Centre de Génétique, CHU de Dijon, Dijon, France ; UF6254 Innovation en Diagnostic Genomique des Maladies Rares, Dijon, France
Tran Mau-Them, Frédéric; Centre de Génétique, CHU de Dijon, Dijon, France ; UF6254 Innovation en Diagnostic Genomique des Maladies Rares, Dijon, France
Maystadt, Isabelle; Centre de Genetique Humaine, Institut de Pathologie et de Genetique, Charleroi, Belgium
Courtin, Thomas; Département de génétique, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, France
Keren, Boris; Département de génétique, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, France
Mouthon, Linda; Département de génétique, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, France
Charles, Perrine; Département de génétique, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, France
Cuinat, Silvestre ; Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, France
Isidor, Bertrand; Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, France
Theis, Philippe; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
Müller, Christian; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
Kulisic, Marizela; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
Türkmen, Seval; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
Stieber, Daniel; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
Bourgeois, Dominique; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
Scalais, Emmanuel; Pediatric Neurology Unit, Pediatric Department, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg
Klink, Barbara; Laboratoire national de santé (LNS), National Center of Genetics (NCG), Dudelange, Luxembourg
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