| Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. | |
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MedLine Citation:
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PMID: 19079258 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Abnormalities in WNT signaling are implicated in a broad range of developmental anomalies and also in tumorigenesis. Here we demonstrate that germline mutations in WTX (FAM123B), a gene that encodes a repressor of canonical WNT signaling, cause an X-linked sclerosing bone dysplasia, osteopathia striata congenita with cranial sclerosis (OSCS; MIM300373). This condition is typically characterized by increased bone density and craniofacial malformations in females and lethality in males. The mouse homolog of WTX is expressed in the fetal skeleton, and alternative splicing implicates plasma membrane localization of WTX as a factor associated with survival in males with OSCS. WTX has also been shown to be somatically inactivated in 11-29% of cases of Wilms tumor. Despite being germline for such mutations, individuals with OSCS are not predisposed to tumor development. The observed phenotypic discordance dependent upon whether a mutation is germline or occurs somatically suggests the existence of temporal or spatial constraints on the action of WTX during tumorigenesis. |
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Authors:
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Zandra A Jenkins; Margriet van Kogelenberg; Tim Morgan; Aaron Jeffs; Ryuji Fukuzawa; Esther Pearl; Christina Thaller; Anne V Hing; Mary E Porteous; Sixto Garcia-Miñaur; Axel Bohring; Didier Lacombe; Fiona Stewart; Torunn Fiskerstrand; Laurence Bindoff; Siren Berland; Lesley C Adès; Michel Tchan; Albert David; Louise C Wilson; Raoul C M Hennekam; Dian Donnai; Sahar Mansour; Valérie Cormier-Daire; Stephen P Robertson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-12-14 |
Journal Detail:
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Title: Nature genetics Volume: 41 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-29 Completed Date: 2009-01-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 95-100 Citation Subset: IM |
Affiliation:
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Departments of Paediatrics, Dunedin School of Medicine, Otago University, Dunedin 9054, New Zealand. |
| Data Bank Information | |
Bank Name/Acc. No.:
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OMIM/MIM300373; RefSeq/NM_175179 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Alternative Splicing / genetics Animals Bone Diseases, Developmental / complications, genetics*, pathology* Child Child, Preschool Chromosome Deletion Chromosomes, Human, Pair 11 / genetics Embryo, Mammalian / metabolism Female Genetic Predisposition to Disease* Germ-Line Mutation / genetics* Humans Infant Male Mice Middle Aged Phenotype Point Mutation Precancerous Conditions / genetics* Protein Structure, Tertiary Sclerosis Tumor Suppressor Proteins / chemistry, genetics* Wilms Tumor / genetics X Chromosome Inactivation / genetics |
| Chemical | |
Reg. No./Substance:
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0/FAM123B protein, human; 0/Tumor Suppressor Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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