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Intellectual disability

Gene: BRD4

Green List (high evidence)

BRD4 (bromodomain containing 4)
EnsemblGeneIds (GRCh38): ENSG00000141867
EnsemblGeneIds (GRCh37): ENSG00000141867
OMIM: 608749, Gene2Phenotype
BRD4 is in 3 panels

3 reviews

Ivone Leong (Genomics England Curator)

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.
Created: 24 Jun 2019, 10:59 a.m. | Last Modified: 24 Jun 2019, 10:59 a.m.
Panel Version: 2.881

Catherine Snow (Genomics England)

Comment on list classification: Addition of gene from reviewer awaiting internal review
Created: 14 May 2019, 10:57 a.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

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 (4/4), other 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 and 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
Created: 24 Nov 2018, 11:57 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Intellectual disability; Microcephaly; Abnormal heart morphology; Abnormality of the face

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Intellectual disability
  • Microcephaly
  • Abnormal heart morphology
  • Abnormality of the face
OMIM
608749
Clinvar variants
Variants in BRD4
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

24 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: brd4 has been classified as Green List (High Evidence).

14 May 2019, Gel status: 1

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: brd4 has been classified as Red List (Low Evidence).

24 Nov 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

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