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Intellectual disability v5.512 BRD4 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Cornelia de Lange syndrome 6, OMIM:620568)
Intellectual disability v5.512 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from Intellectual disability; Microcephaly; Abnormal heart morphology; Abnormality of the face to Cornelia de Lange syndrome 6, OMIM:620568
Intellectual disability v5.511 BRD4 Arina Puzriakova Tag gene-checked was removed from gene: BRD4.
Intellectual disability v3.1561 BRD4 Sarah Leigh Tag gene-checked tag was added to gene: BRD4.
Intellectual disability v2.881 BRD4 Ivone Leong Classified gene: BRD4 as Green List (high evidence)
Intellectual disability v2.881 BRD4 Ivone Leong Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team. Promoted from red to green based on the evidence provided by Konstantinos Varvagiannis (Other). BRD4 is not associated with a phenotype in OMIM and in Gene2Phenotype it is reported to be probably associated with Cornelia de Lange-like syndrome. Intellectual disability (medium to severe) is a phenotype of Cornelia de Lange-like syndrome.
Intellectual disability v2.881 BRD4 Ivone Leong Gene: brd4 has been classified as Green List (High Evidence).
Intellectual disability v2.818 BRD4 Catherine Snow Classified gene: BRD4 as Red List (low evidence)
Intellectual disability v2.818 BRD4 Catherine Snow Added comment: Comment on list classification: Addition of gene from reviewer awaiting internal review
Intellectual disability v2.818 BRD4 Catherine Snow Gene: brd4 has been classified as Red List (Low Evidence).
Intellectual disability v2.555 BRD4 Konstantinos Varvagiannis gene: BRD4 was added
gene: BRD4 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: BRD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BRD4 were set to 29379197; 30055032; 30302754
Phenotypes for gene: BRD4 were set to Intellectual disability; Microcephaly; Abnormal heart morphology; Abnormality of the face
Penetrance for gene: BRD4 were set to unknown
Review for gene: BRD4 was set to GREEN
gene: BRD4 was marked as current diagnostic
Added comment: PMID: 29379197 reports on 3 unrelated individuals with de novo mutations in BRD4 and a Cornelia de Lange-like phenotype. One of these individuals was a DDD study participant (DDD4K.04273). A further (fourth) individual had a 1.04 Mb deletion encompassing BRD4 (and 28 other genes) and presented with a similar phenotype.

Appart from intellectual disability which was a universal feature common features included a CdLS-like appearance (3/4), microcephaly (3/4) and cardiac malformations (VSD in 2/4).

Review of published patients with multigenic deletions spanning also BRD4 support a CdLS-like phenotype as well as haploinsufficiency as the underlying mechanism.

As the authors note, mice heterozygous for loss-of-function mutations in BRD4 show CdLS like features.
Functional studies performed demonstrated association of BRD4 with NIPBL with colocalization (/shared binding) to super-enhancers and co-regulation of gene expression.

The variants reported in this study included a missense as well as 2 frameshift mutations.

PMIDs: 30055032 and 30302754 report further patients with deletions spanning BRD4 and review the previously published patients.

BRD4 is included in gene panels for intellectual disability offered by different diagnostic laboratories.

As a result this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review