Understanding the new BRD4-related syndrome: Clinical and genomic delineation with an international cohort study

Guillaume Jouret*, Solveig Heide, Arthur Sorlin, Laurence Faivre, Sandra Chantot-Bastaraud, Claire Beneteau, Marie Denis-Musquer, Peter D. Turnpenny, Charles Coutton, Gaëlle Vieville, Julien Thevenon, Austin Larson, Florence Petit, Elise Boudry, Thomas Smol, Bruno Delobel, Bénédicte Duban-Bedu, Chiara Fallerini, Francesca Mari, Caterina Lo RizzoAlessandra Renieri, Jean Hubert Caberg, Anne Sophie Denommé-Pichon, Frédéric Tran Mau-Them, Isabelle Maystadt, Thomas Courtin, Boris Keren, Linda Mouthon, Perrine Charles, Silvestre Cuinat, Bertrand Isidor, Philippe Theis, Christian Müller, Marizela Kulisic, Seval Türkmen, Daniel Stieber, Dominique Bourgeois, Emmanuel Scalais, Barbara Klink

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalClinical Genetics
Volume102
Issue number2
DOIs
Publication statusPublished - Aug 2022
Externally publishedYes

Keywords

  • BRD4
  • BRD4-related syndrome
  • Cornelia de Lange syndrome
  • NIPBL
  • cohesinopathy

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