Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation.
In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found at the cytoplasmic face of coated vesicles located at the Golgi complex. The complex mediates the recruitment of clathrin to the vesicle membrane. Aberrant endocytic processing through disruption of adaptor protein complexes is likely to result from the AP1S2 mutations identified in the three XLMR-affected families, and such defects may plausibly cause abnormal synaptic development and function. AP1S2 is the first reported XLMR gene that encodes a protein directly involved in the assembly of endocytic vesicles.
Tarpey
Patrick S
PS
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Stevens
Claire
C
Teague
Jon
J
Edkins
Sarah
S
O'Meara
Sarah
S
Avis
Tim
T
Barthorpe
Syd
S
Buck
Gemma
G
Butler
Adam
A
Cole
Jennifer
J
Dicks
Ed
E
Gray
Kristian
K
Halliday
Kelly
K
Harrison
Rachel
R
Hills
Katy
K
Hinton
Jonathon
J
Jones
David
D
Menzies
Andrew
A
Mironenko
Tatiana
T
Perry
Janet
J
Raine
Keiran
K
Richardson
David
D
Shepherd
Rebecca
R
Small
Alexandra
A
Tofts
Calli
C
Varian
Jennifer
J
West
Sofie
S
Widaa
Sara
S
Yates
Andy
A
Catford
Rachael
R
Butler
Julia
J
Mallya
Uma
U
Moon
Jenny
J
Luo
Ying
Y
Dorkins
Huw
H
Thompson
Deborah
D
Easton
Douglas F
DF
Wooster
Richard
R
Bobrow
Martin
M
Carpenter
Nancy
N
Simensen
Richard J
RJ
Schwartz
Charles E
CE
Stevenson
Roger E
RE
Turner
Gillian
G
Partington
Michael
M
Gecz
Jozef
J
Stratton
Michael R
MR
Futreal
P Andrew
PA
Raymond
F Lucy
FL
D034002:Adaptor Protein Complex sigma Subunits / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D002648:Child; D011992:Endosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000209:etiology / Q000235:genetics* / Q000523:psychology; D009154:Mutation; D010375:Pedigree
C516800:AP1S2 protein, human; D034002:Adaptor Protein Complex sigma Subunits