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.
Field
Michael
M
GOLD Service, Hunter Genetics, Waratah, Australia.
Tarpey
Patrick S
PS
Smith
Raffaella
R
Edkins
Sarah
S
O'Meara
Sarah
S
Stevens
Claire
C
Tofts
Calli
C
Teague
Jon
J
Butler
Adam
A
Dicks
Ed
E
Barthorpe
Syd
S
Buck
Gemma
G
Cole
Jennifer
J
Gray
Kristian
K
Halliday
Kelly
K
Hills
Katy
K
Jenkinson
Andrew
A
Jones
David
D
Menzies
Andrew
A
Mironenko
Tatiana
T
Perry
Janet
J
Raine
Keiran
K
Richardson
David
D
Shepherd
Rebecca
R
Small
Alexandra
A
Varian
Jennifer
J
West
Sofie
S
Widaa
Sara
S
Mallya
Uma
U
Wooster
Richard
R
Moon
Jenny
J
Luo
Ying
Y
Hughes
Helen
H
Shaw
Marie
M
Friend
Kathryn L
KL
Corbett
Mark
M
Turner
Gillian
G
Partington
Michael
M
Mulley
John
J
Bobrow
Martin
M
Schwartz
Charles
C
Stevenson
Roger
R
Gecz
Jozef
J
Stratton
Michael R
MR
Futreal
P Andrew
PA
Raymond
F Lucy
FL
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