Document Detail

Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1.
MedLine Citation:
PMID:  9288098     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature genetics     Volume:  17     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-10-02     Completed Date:  1997-10-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  58-64     Citation Subset:  IM    
Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Amino Acid Sequence
Base Sequence
Bone Morphogenetic Proteins*
COS Cells
Conserved Sequence
Dwarfism / genetics
Fingers / abnormalities
Genes, Dominant
Genes, Recessive
Growth Differentiation Factor 5
Growth Substances / biosynthesis,  chemistry,  genetics*
Hand Deformities, Congenital / genetics
Osteochondrodysplasias / genetics*
Point Mutation*
Recombinant Proteins / biosynthesis,  chemistry
Grant Support
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Growth Differentiation Factor 5; 0/Growth Substances; 0/Recombinant Proteins; 52-90-4/Cysteine; 55520-40-6/Tyrosine

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