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Type: Journal article
Title: Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation
Author: Tarpey, P.
Raymond, F.
Nguyen, L.
Rodriguez, J.
Hackett, A.
Vandeleur, L.
Smith, R.
Shoubridge, C.
Edkins, S.
Stevens, C.
O'Meara, S.
Tofts, C.
Barthorpe, S.
Buck, G.
Cole, J.
Halliday, K.
Hills, K.
Jones, D.
Mironenko, T.
Perry, J.
et al.
Citation: Nature Genetics, 2007; 39(9):1127-1133
Publisher: Nature Publishing Group
Issue Date: 2007
ISSN: 1061-4036
Organisation: Centre for the Molecular Genetics of Development
Statement of
Patrick S Tarpey, F Lucy Raymond, Lam S Nguyen, Jayson Rodriguez, Anna Hackett, Lucianne Vandeleur, Raffaella Smith, Cheryl Shoubridge, Sarah Edkins, Claire Stevens, Sarah O'Meara, Calli Tofts, Syd Barthorpe, Gemma Buck, Jennifer Cole, Kelly Halliday, Katy Hills, David Jones, Tatiana Mironenko, Janet Perry, Jennifer Varian, Sofie West, Sara Widaa, John Teague, Ed Dicks, Adam Butler, Andrew Menzies, David Richardson, Andrew Jenkinson, Rebecca Shepherd, Keiran Raine, Jenny Moon, Yin Luo, Josep Parnau, Shambhu S Bhat, Alison Gardner, Mark Corbett, Doug Brooks, Paul Thomas, Emma Parkinson-Lawrence, Mary E Porteous, John P Warner, Tracy Sanderson, Pauline Pearson, Richard J Simensen, Cindy Skinner, George Hoganson, Duane Superneau, Richard Wooster, Martin Bobrow, Gillian Turner, Roger E Stevenson, Charles E Schwartz, P Andrew Futreal, Anand K Srivastava, Michael R Stratton & Jozef Gécz
Abstract: Nonsense-mediated mRNA decay (NMD) is of universal biological significance1, 2, 3. It has emerged as an important global RNA, DNA and translation regulatory pathway4. 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 phenotype5, 6 and one with the FG phenotype7. 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 machinery8, 9. Our results directly implicate abnormalities of NMD in human disease and suggest at least partial redundancy of NMD pathways.
Keywords: Humans
Mental Retardation, X-Linked
RNA-Binding Proteins
Gene Expression Profiling
Reverse Transcriptase Polymerase Chain Reaction
DNA Mutational Analysis
Sequence Homology, Amino Acid
Amino Acid Sequence
Family Health
Molecular Sequence Data
Codon, Nonsense
Cell Line, Transformed
RNA Stability
RNA, Messenger
Rights: © 2007 Nature Publishing Group
DOI: 10.1038/ng2100
Published version:
Appears in Collections:Aurora harvest
Centre for the Molecular Genetics of Development publications
Molecular and Biomedical Science publications

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