Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders
Gene: BRWD3
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 300659Created: 28 Apr 2018, 12:36 p.m.
Sufficient cases, appropriate phenotypeCreated: 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
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 soonCreated: 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From abstract (unpublished) Tatton-Brown et al (2017)(http://conf.hinxton.wellcome.ac.uk/advancedcourses/GRD2017Abstactbook.pdf) Human overgrowth syndromes (OGID) are a nebulous group of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
Phenotypes for gene: BRWD3 were changed from Mental retardation, X-linked 93, 300659; macrocephaly to Mental retardation, X-linked 93, 300659; macrocephaly; intellectual disability
Phenotypes for gene: BRWD3 were changed from Mental retardation, X-linked 93 300659 to Mental retardation, X-linked 93, 300659; macrocephaly
Publications for gene: BRWD3 were set to
This gene has been classified as Green List (High Evidence).
Phenotypes for BRWD3 were set to Mental retardation, X-linked 93 300659
Phenotypes for BRWD3 were set to Human overgrowth syndrome type
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)
This gene has been classified as Green List (High Evidence).
BRWD3 was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorderspanel. Sources: Other
BRWD3 was created by LouiseD