title: Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus.
abstract: We have identified one frameshift mutation, one splice-site mutation, and two missense mutations in highly conserved residues in ZDHHC9 at Xq26.1 in 4 of 250 families with X-linked mental retardation (XLMR). In three of the families, the mental retardation phenotype is associated with a Marfanoid habitus, although none of the affected individuals meets the Ghent criteria for Marfan syndrome. ZDHHC9 is a palmitoyltransferase that catalyzes the posttranslational modification of NRAS and HRAS. The degree of palmitoylation determines the temporal and spatial location of these proteins in the plasma membrane and Golgi complex. The finding of mutations in ZDHHC9 suggests that alterations in the concentrations and cellular distribution of target proteins are sufficient to cause disease. This is the first XLMR gene to be reported that encodes a posttranslational modification enzyme, palmitoyltransferase. Furthermore, now that the first palmitoyltransferase that causes mental retardation has been identified, defects in other palmitoylation transferases become good candidates for causing other mental retardation syndromes.
authors: Cambridge Institute of Medical Research, University of Cambridge, Cambridge, CB2 2XY, UK. flr24@cam.ac.uk.
authors: F Lucy
authors: FL
authors: Raymond
authors: Patrick S
authors: PS
authors: Tarpey
authors: Sarah
authors: S
authors: Edkins
authors: Calli
authors: C
authors: Tofts
authors: Sarah
authors: S
authors: O'Meara
authors: Jon
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authors: Teague
authors: Adam
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authors: Butler
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authors: Stevens
authors: Syd
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authors: Barthorpe
authors: Gemma
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authors: Buck
authors: Jennifer
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authors: Cole
authors: Ed
authors: E
authors: Dicks
authors: Kristian
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authors: Gray
authors: Kelly
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authors: Halliday
authors: Katy
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authors: Hills
authors: Jonathon
authors: J
authors: Hinton
authors: David
authors: D
authors: Jones
authors: Andrew
authors: A
authors: Menzies
authors: Janet
authors: J
authors: Perry
authors: Keiran
authors: K
authors: Raine
authors: Rebecca
authors: R
authors: Shepherd
authors: Alexandra
authors: A
authors: Small
authors: Jennifer
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authors: Varian
authors: Sara
authors: S
authors: Widaa
authors: Uma
authors: U
authors: Mallya
authors: Jenny
authors: J
authors: Moon
authors: Ying
authors: Y
authors: Luo
authors: Marie
authors: M
authors: Shaw
authors: Jackie
authors: J
authors: Boyle
authors: Bronwyn
authors: B
authors: Kerr
authors: Gillian
authors: G
authors: Turner
authors: Oliver
authors: O
authors: Quarrell
authors: Trevor
authors: T
authors: Cole
authors: Douglas F
authors: DF
authors: Easton
authors: Richard
authors: R
authors: Wooster
authors: Martin
authors: M
authors: Bobrow
authors: Charles E
authors: CE
authors: Schwartz
authors: Jozef
authors: J
authors: Gecz
authors: Michael R
authors: MR
authors: Stratton
authors: P Andrew
authors: PA
authors: Futreal
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D038901:X-Linked Intellectual Disability / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D018631:ras Proteins / Q000378:metabolism
chemical_list: D004247:DNA; D000217:Acyltransferases; C504825:ZDHHC9 protein, human; D018631:ras Proteins