title: Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation.
abstract: Nonsense-mediated mRNA decay (NMD) is of universal biological significance. It has emerged as an important global RNA, DNA and translation regulatory pathway. By systematically sequencing 737 genes (annotated in the Vertebrate Genome Annotation database) on the human X chromosome in 250 families with X-linked mental retardation, we identified mutations in the UPF3 regulator of nonsense transcripts homolog B (yeast) (UPF3B) leading to protein truncations in three families: two with the Lujan-Fryns phenotype and one with the FG phenotype. We also identified a missense mutation in another family with nonsyndromic mental retardation. Three mutations lead to the introduction of a premature termination codon and subsequent NMD of mutant UPF3B mRNA. Protein blot analysis using lymphoblastoid cell lines from affected individuals showed an absence of the UPF3B protein in two families. The UPF3B protein is an important component of the NMD surveillance machinery. Our results directly implicate abnormalities of NMD in human disease and suggest at least partial redundancy of NMD pathways.
authors: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors: Patrick S
authors: PS
authors: Tarpey
authors: F Lucy
authors: FL
authors: Raymond
authors: Lam S
authors: LS
authors: Nguyen
authors: Jayson
authors: J
authors: Rodriguez
authors: Anna
authors: A
authors: Hackett
authors: Lucianne
authors: L
authors: Vandeleur
authors: Raffaella
authors: R
authors: Smith
authors: Cheryl
authors: C
authors: Shoubridge
authors: Sarah
authors: S
authors: Edkins
authors: Claire
authors: C
authors: Stevens
authors: Sarah
authors: S
authors: O'Meara
authors: Calli
authors: C
authors: Tofts
authors: Syd
authors: S
authors: Barthorpe
authors: Gemma
authors: G
authors: Buck
authors: Jennifer
authors: J
authors: Cole
authors: Kelly
authors: K
authors: Halliday
authors: Katy
authors: K
authors: Hills
authors: David
authors: D
authors: Jones
authors: Tatiana
authors: T
authors: Mironenko
authors: Janet
authors: J
authors: Perry
authors: Jennifer
authors: J
authors: Varian
authors: Sofie
authors: S
authors: West
authors: Sara
authors: S
authors: Widaa
authors: John
authors: J
authors: Teague
authors: Ed
authors: E
authors: Dicks
authors: Adam
authors: A
authors: Butler
authors: Andrew
authors: A
authors: Menzies
authors: David
authors: D
authors: Richardson
authors: Andrew
authors: A
authors: Jenkinson
authors: Rebecca
authors: R
authors: Shepherd
authors: Keiran
authors: K
authors: Raine
authors: Jenny
authors: J
authors: Moon
authors: Yin
authors: Y
authors: Luo
authors: Josep
authors: J
authors: Parnau
authors: Shambhu S
authors: SS
authors: Bhat
authors: Alison
authors: A
authors: Gardner
authors: Mark
authors: M
authors: Corbett
authors: Doug
authors: D
authors: Brooks
authors: Paul
authors: P
authors: Thomas
authors: Emma
authors: E
authors: Parkinson-Lawrence
authors: Mary E
authors: ME
authors: Porteous
authors: John P
authors: JP
authors: Warner
authors: Tracy
authors: T
authors: Sanderson
authors: Pauline
authors: P
authors: Pearson
authors: Richard J
authors: RJ
authors: Simensen
authors: Cindy
authors: C
authors: Skinner
authors: George
authors: G
authors: Hoganson
authors: Duane
authors: D
authors: Superneau
authors: Richard
authors: R
authors: Wooster
authors: Martin
authors: M
authors: Bobrow
authors: Gillian
authors: G
authors: Turner
authors: Roger E
authors: RE
authors: Stevenson
authors: Charles E
authors: CE
authors: Schwartz
authors: P Andrew
authors: PA
authors: Futreal
authors: Anand K
authors: AK
authors: Srivastava
authors: Michael R
authors: MR
authors: Stratton
authors: Jozef
authors: J
authors: Gécz
mesh_terms: D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C435488:UPF3B protein, human
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