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Microcephaly

Gene: BRD4

Green List (high evidence)

BRD4 (bromodomain containing 4)
EnsemblGeneIds (GRCh38): ENSG00000141867
EnsemblGeneIds (GRCh37): ENSG00000141867
OMIM: 608749, Gene2Phenotype
BRD4 is in 6 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Sufficient individuals with microcephaly to support Green rating on this panel.

Cornelia de Lange syndrome is a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems. Affected individuals have dysmorphic facial features, cleft palate, distal limb defects, growth retardation, and developmental delay. About 1% of patients have mutations in the BRD4 gene.

Olley et al. (2018) report 4 patients with CdLS phenotype with 4 different variants (1 deletion incl BRD4, 1 missense, and 2 frameshift). Alesi et al. (2019) reported a patient with 19p13.12p13.11 deletion including BRD4 with CdLS phenotype.

Olley et al (2021) provided further functional evidence for the previous missense variant, showing it reduces BRD4-occupancy at enhancers it does not affect transcription of the pluripotency network in mouse embryonic stem cells. Rather, it delays the cell cycle, increases DNA damage signalling, and perturbs regulation of DNA repair in mutant cells.

Houzelstein et al. (2002) showed that mice with heterozygous LOF mutations in Brd4 have marked early postnatal mortality, severe prenatal onset growth failure, abnormalities of the craniofacial skeleton and reduced body fat19; all features common in CdLS.
Created: 20 Aug 2021, 12:07 a.m. | Last Modified: 20 Aug 2021, 12:07 a.m.
Panel Version: 1.40

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cornelia de Lange syndrome 6, MIM# 620568

Publications

Ain Roesley (Victorian Clinical Genetics Services)

I don't know

PMID: 29379197;
- 4x patients reports however only 3 reported with occipitofrontal circumference of < -3 SD
- 1x microdeletion of 1.04Mb, 1x missense and 1x fs. All de novo

PMID: 30302754
- 1x proband with occipitofrontal circumference 28 cm (−2 SD)
- de novo interstitial deletion involving the shortarm of a chromosome 19, 1.97 Mb in size, which included BRD4
Created: 31 Aug 2020, 7:42 a.m. | Last Modified: 31 Aug 2020, 7:42 a.m.
Panel Version: 0.213

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

Phenotypes
Cornelia de Lange-like syndrome

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Cornelia de Lange syndrome 6, MIM# 620568
Tags
SV/CNV
OMIM
608749
Clinvar variants
Variants in BRD4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Dec 2023, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome, MONDO:0016033 to Cornelia de Lange syndrome 6, MIM# 620568

24 Feb 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: BRD4 were changed from Cornelia de Lange-like syndrome to Cornelia de Lange-like syndrome, MONDO:0016033

20 Aug 2021, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: BRD4 were set to 29379197; 30302754

20 Aug 2021, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

31 Aug 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: brd4 has been classified as Amber List (Moderate Evidence).

31 Aug 2020, Gel status: 2

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag SV/CNV tag was added to gene: BRD4.

31 Aug 2020, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: BRD4 were changed from to Cornelia de Lange-like syndrome

31 Aug 2020, Gel status: 2

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: BRD4 were set to

31 Aug 2020, Gel status: 2

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: BRD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

31 Aug 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: brd4 has been classified as Amber List (Moderate Evidence).

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: BRD4 was added gene: BRD4 was added to Microcephaly_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: BRD4 was set to Unknown