Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly.
In the course of systematic screening of the X-chromosome coding sequences in 250 families with nonsyndromic X-linked mental retardation (XLMR), two families were identified with truncating mutations in BRWD3, a gene encoding a bromodomain and WD-repeat domain-containing protein. In both families, the mutation segregates with the phenotype in affected males. Affected males have macrocephaly with a prominent forehead, large cupped ears, and mild-to-moderate intellectual disability. No truncating variants were found in 520 control X chromosomes. BRWD3 is therefore a new gene implicated in the etiology of XLMR associated with macrocephaly and may cause disease by altering intracellular signaling pathways affecting cellular proliferation.
GOLD Service, Hunter Genetics, Waratah, Australia.
Michael
M
Field
Patrick S
PS
Tarpey
Raffaella
R
Smith
Sarah
S
Edkins
Sarah
S
O'Meara
Claire
C
Stevens
Calli
C
Tofts
Jon
J
Teague
Adam
A
Butler
Ed
E
Dicks
Syd
S
Barthorpe
Gemma
G
Buck
Jennifer
J
Cole
Kristian
K
Gray
Kelly
K
Halliday
Katy
K
Hills
Andrew
A
Jenkinson
David
D
Jones
Andrew
A
Menzies
Tatiana
T
Mironenko
Janet
J
Perry
Keiran
K
Raine
David
D
Richardson
Rebecca
R
Shepherd
Alexandra
A
Small
Jennifer
J
Varian
Sofie
S
West
Sara
S
Widaa
Uma
U
Mallya
Richard
R
Wooster
Jenny
J
Moon
Ying
Y
Luo
Helen
H
Hughes
Marie
M
Shaw
Kathryn L
KL
Friend
Mark
M
Corbett
Gillian
G
Turner
Michael
M
Partington
John
J
Mulley
Martin
M
Bobrow
Charles
C
Schwartz
Roger
R
Stevenson
Jozef
J
Gecz
Michael R
MR
Stratton
P Andrew
PA
Futreal
F Lucy
FL
Raymond
D000015:Abnormalities, Multiple / Q000235:genetics*; D006257:Head / Q000002:abnormalities*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
D014157:Transcription Factors; C502037:BRWD3 protein, human; D000092468:Bromodomain Containing Proteins