Gene under study
BRD4, OMIM 608749
Abstract
BRD4 is a component of a multiprotein complex essential for the loading of the cohesin complex onto DNA — a critical step in cohesin-mediated loop extrusion and the establishment of Topologically Associating Domains. Pathogenic variants in genes encoding members of this complex have been implicated in an expanding group of syndromes collectively referred to as cohesinopathies, the prototypical example being Cornelia de Lange syndrome.
In 2022, our team published the first cohort of individuals affected by a BRD4-related disorder, participating in establishing this condition as a new clinically recognized member of the cohesinopathy spectrum. Despite this progress, the episignature associated with BRD4-related disorder remains undefined.
We are currently establishing a new international cohort of individuals harboring pathogenic or likely pathogenic variants in BRD4, with the goal of identifying a disease-specific DNA methylation episignature. This work could not only contribute a valuable biomarker to improve variant interpretation and diagnostic precision, but also enhance our understanding of the underlying disease mechanisms.
Coordinating clinician
Dr Guillaume Jouret – guillaume.jouret@lns.etat.lu
Institution
National Center of Genetics (NCG), Laboratoire national de santé (LNS), Dudelange, Luxembourg
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: Yes
2- Resampling of patients: No
3- Linked to a translational/basic research project: Yes