title: Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation.
abstract: 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.
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tarpey
authors.forename: Claire
authors.initials: C
authors.lastname: Stevens
authors.forename: Jon
authors.initials: J
authors.lastname: Teague
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Sarah
authors.initials: S
authors.lastname: O'Meara
authors.forename: Tim
authors.initials: T
authors.lastname: Avis
authors.forename: Syd
authors.initials: S
authors.lastname: Barthorpe
authors.forename: Gemma
authors.initials: G
authors.lastname: Buck
authors.forename: Adam
authors.initials: A
authors.lastname: Butler
authors.forename: Jennifer
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authors.lastname: Cole
authors.forename: Ed
authors.initials: E
authors.lastname: Dicks
authors.forename: Kristian
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authors.forename: Kelly
authors.initials: K
authors.lastname: Halliday
authors.forename: Rachel
authors.initials: R
authors.lastname: Harrison
authors.forename: Katy
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authors.lastname: Hills
authors.forename: Jonathon
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authors.lastname: Hinton
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.forename: Andrew
authors.initials: A
authors.lastname: Menzies
authors.forename: Tatiana
authors.initials: T
authors.lastname: Mironenko
authors.forename: Janet
authors.initials: J
authors.lastname: Perry
authors.forename: Keiran
authors.initials: K
authors.lastname: Raine
authors.forename: David
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authors.lastname: Richardson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shepherd
authors.forename: Alexandra
authors.initials: A
authors.lastname: Small
authors.forename: Calli
authors.initials: C
authors.lastname: Tofts
authors.forename: Jennifer
authors.initials: J
authors.lastname: Varian
authors.forename: Sofie
authors.initials: S
authors.lastname: West
authors.forename: Sara
authors.initials: S
authors.lastname: Widaa
authors.forename: Andy
authors.initials: A
authors.lastname: Yates
authors.forename: Rachael
authors.initials: R
authors.lastname: Catford
authors.forename: Julia
authors.initials: J
authors.lastname: Butler
authors.forename: Uma
authors.initials: U
authors.lastname: Mallya
authors.forename: Jenny
authors.initials: J
authors.lastname: Moon
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.forename: Huw
authors.initials: H
authors.lastname: Dorkins
authors.forename: Deborah
authors.initials: D
authors.lastname: Thompson
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Richard
authors.initials: R
authors.lastname: Wooster
authors.forename: Martin
authors.initials: M
authors.lastname: Bobrow
authors.forename: Nancy
authors.initials: N
authors.lastname: Carpenter
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simensen
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Roger E
authors.initials: RE
authors.lastname: Stevenson
authors.forename: Gillian
authors.initials: G
authors.lastname: Turner
authors.forename: Michael
authors.initials: M
authors.lastname: Partington
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: F Lucy
authors.initials: FL
authors.lastname: Raymond
mesh_terms: 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
chemical_list: C516800:AP1S2 protein, human; D034002:Adaptor Protein Complex sigma Subunits