| Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. | |
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MedLine Citation:
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PMID: 9288098 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chondrodysplasia Grebe type (CGT) is an autosomal recessive disorder characterized by severe limb shortening and dysmorphogenesis. We have identified a causative point mutation in the gene encoding the bone morphogenetic protein (BMP)-like molecule, cartilage-derived morphogenetic protein-1 (CDMP-1). The mutation substitutes a tyrosine for the first of seven highly conserved cysteine residues in the mature active domain of the protein. We demonstrate that the mutation results in a protein that is not secreted and is inactive in vitro. It produces a dominant negative effect by preventing the secretion of other, related BMP family members. We present evidence that this may occur through the formation of heterodimers. The mutation and its proposed mechanism of action provide the first human genetic indication that composite expression patterns of different BMPs dictate limb and digit morphogenesis. |
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Authors:
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J T Thomas; M W Kilpatrick; K Lin; L Erlacher; P Lembessis; T Costa; P Tsipouras; F P Luyten |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Nature genetics Volume: 17 ISSN: 1061-4036 ISO Abbreviation: Nat. Genet. Publication Date: 1997 Sep |
Date Detail:
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Created Date: 1997-10-02 Completed Date: 1997-10-02 Revised Date: 2008-11-21 |
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: 58-64 Citation Subset: IM |
Affiliation:
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Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. tthomas@yoda.nidr.nih.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Base Sequence Bone Morphogenetic Proteins* COS Cells Conserved Sequence Cysteine Dwarfism / genetics Female Fingers / abnormalities Genes, Dominant Genes, Recessive Growth Differentiation Factor 5 Growth Substances / biosynthesis, chemistry, genetics* Hand Deformities, Congenital / genetics Heterozygote Humans Male Morphogenesis Osteochondrodysplasias / genetics* Pedigree Point Mutation* Recombinant Proteins / biosynthesis, chemistry Transfection Tyrosine |
| Grant Support | |
ID/Acronym/Agency:
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HD-22610/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bone Morphogenetic Proteins; 0/Growth Differentiation Factor 5; 0/Growth Substances; 0/Recombinant Proteins; 52-90-4/Cysteine; 55520-40-6/Tyrosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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