Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders

Gene: BRWD3

Green List (high evidence)

BRWD3 (bromodomain and WD repeat domain containing 3)
EnsemblGeneIds (GRCh38): ENSG00000165288
EnsemblGeneIds (GRCh37): ENSG00000165288
OMIM: 300553, Gene2Phenotype
BRWD3 is in 4 panels

2 reviews

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Comment when marking as ready: Mild - moderate ID associated with tall stature and macrocephaly. Sufficient cases.
Created: 28 Apr 2018, 12:37 p.m.
Comment on phenotypes: Mental retardation, X-linked 93 300659
Created: 28 Apr 2018, 12:36 p.m.
Sufficient cases, appropriate phenotype
Created: 28 Apr 2018, 12:35 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Mental retardation, X-linked 93 300659

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Review and Green rating from Kate Tatton-Brown April 2017. The paper is in press with American Journal of Human Genetics. Mutations in BRWD3 cause macrocephaly rather than overgrowth per se. We wil be reporting variants in clinical practice soon
Created: 31 May 2019, 9:05 a.m.
Recently Human overgrowth syndrome-causing mutations in the gene BRWD3 have been identified.
From abstract (unpublished) Tatton-Brown et al (2017)(http://conf.hinxton.wellcome.ac.uk/advancedcourses/GRD2017Abstactbook.pdf) Human overgrowth syndromes (OGID) are a nebulous group of conditions with height and/or head circumference ≥ 2SD above the mean, together with additional phenotypic abnormalities, the commonest of which is intellectual disability. To explore the genetic architecture of human overgrowth syndromes and growth control, we have performed experimental and bioinformatic analyses of 710 individuals with OGID, identifying patients with OGID-causing mutations in genes including NSD1 (240 cases), EZH2 (34 cases), DNMT3A (18 cases), CHD8 (12 cases) and EED (two cases) and HIST1H1E (five cases). Other genes with OGID-causing mutations, identified in the current study, include NFIX (14 cases), GPC3 (two cases) and BRWD3 (seven cases) in addition to the genes encoding components of the PI3K/AKT pathway (PTEN (16 cases); PPP2R5D (three cases); AKT and PIK3CA (one case each).
Created: 31 Mar 2017, 5:59 p.m.

Mode of inheritance
Unknown

Phenotypes
Human overgrowth syndrome type

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Other
Phenotypes
  • Mental retardation, X-linked 93, 300659
  • macrocephaly
  • intellectual disability
OMIM
300553
Clinvar variants
Variants in BRWD3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

31 May 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: BRWD3 were changed from Mental retardation, X-linked 93, 300659; macrocephaly to Mental retardation, X-linked 93, 300659; macrocephaly; intellectual disability

31 May 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: BRWD3 were changed from Mental retardation, X-linked 93 300659 to Mental retardation, X-linked 93, 300659; macrocephaly

31 May 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: BRWD3 were set to

28 Apr 2018, Gel status: 3

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

28 Apr 2018, Gel status: 3

Set Phenotypes

Helen Brittain (Genomics England Curator)

Phenotypes for BRWD3 were set to Mental retardation, X-linked 93 300659

28 Apr 2018, Gel status: 3

Set Phenotypes

Helen Brittain (Genomics England Curator)

Phenotypes for BRWD3 were set to Human overgrowth syndrome type

28 Apr 2018, Gel status: 3

Set mode of inheritance

Helen Brittain (Genomics England Curator)

Mode of inheritance for BRWD3 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

28 Apr 2018, Gel status: 3

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

31 Mar 2017, Gel status: 0

Added New Source

Louise Daugherty (Genomics England Curator)

BRWD3 was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorderspanel. Sources: Other

31 Mar 2017, Gel status: 0

Created

Louise Daugherty (Genomics England Curator)

BRWD3 was created by LouiseD