Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Mutations in collagen genes: causes of rare and some common diseases in humans

Mutations in collagen genes: causes of rare and some common diseases in humans More than 70 mutations in the two structural genes for type I procollagen (COL1A1 and COL1A2) have been found in probands with osteogenesis imperfecta, a heritable disease of children characterized by fragility of bone and other tissues rich in type I collagen. The mutations include deletions, insertions, RNA splicing mutations, and single‐base substitutions that convert a codon for glycine to a codon for an amino acid with a bulkier side chain. With a few exceptions, the most severe phenotypes of the disease are explained largely by synthesis of structurally defective proa chains of type I procollagen that either interfere with the folding of the triple helix or with self‐assembly of collagen into fibrils. The results emphasize the extent to which the zipperlike folding of the collagen triple helix and the self‐assembly of collagen fibrils depend on the principle of nucleated growth whereby a few subunits form a nucleus and the nucleus is then propagated to generate a large structure with a precisely defined architecture. The principle of nucleated growth is a highly efficient mechanism for the assembly of large structures, but biological systems that depend extensively on nucleated growth are highly vulnerable to mutations that cause synthesis of structurally abnormal but partially functional subunits. Recently, several mutations in three other collagen genes (COL2A1, COL3A1, and COL4A5) have been found in probands with genetic diseases involving tissues rich in these collagens. Most of the probands have rare genetic diseases but a few appear to have phenotypes that are difficult to distinguish from more common disorders such as osteoarthritis, osteoporosis, and aortic aneurysms. Therefore, the results suggest that mutations in procollagen genes may cause a wide spectrum of both rare and common human diseases.—Kuivaniemi, H.; Tromp, G.; Prockop, D. J. Mutations in collagen genes: causes of rare and some common diseases in humans. FASEB J. 5: 2052–2060; 1991. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The FASEB journal Wiley

Mutations in collagen genes: causes of rare and some common diseases in humans

Download PDF
9 pages

Loading next page...
 
/lp/wiley/mutations-in-collagen-genes-causes-of-rare-and-some-common-diseases-in-zAT94dQ3yX

References (36)

Publisher
Wiley
Copyright
© Federation of American Societies for Experimental Biology
ISSN
0892-6638
eISSN
1530-6860
DOI
10.1096/fasebj.5.7.2010058
Publisher site
See Article on Publisher Site

Abstract

More than 70 mutations in the two structural genes for type I procollagen (COL1A1 and COL1A2) have been found in probands with osteogenesis imperfecta, a heritable disease of children characterized by fragility of bone and other tissues rich in type I collagen. The mutations include deletions, insertions, RNA splicing mutations, and single‐base substitutions that convert a codon for glycine to a codon for an amino acid with a bulkier side chain. With a few exceptions, the most severe phenotypes of the disease are explained largely by synthesis of structurally defective proa chains of type I procollagen that either interfere with the folding of the triple helix or with self‐assembly of collagen into fibrils. The results emphasize the extent to which the zipperlike folding of the collagen triple helix and the self‐assembly of collagen fibrils depend on the principle of nucleated growth whereby a few subunits form a nucleus and the nucleus is then propagated to generate a large structure with a precisely defined architecture. The principle of nucleated growth is a highly efficient mechanism for the assembly of large structures, but biological systems that depend extensively on nucleated growth are highly vulnerable to mutations that cause synthesis of structurally abnormal but partially functional subunits. Recently, several mutations in three other collagen genes (COL2A1, COL3A1, and COL4A5) have been found in probands with genetic diseases involving tissues rich in these collagens. Most of the probands have rare genetic diseases but a few appear to have phenotypes that are difficult to distinguish from more common disorders such as osteoarthritis, osteoporosis, and aortic aneurysms. Therefore, the results suggest that mutations in procollagen genes may cause a wide spectrum of both rare and common human diseases.—Kuivaniemi, H.; Tromp, G.; Prockop, D. J. Mutations in collagen genes: causes of rare and some common diseases in humans. FASEB J. 5: 2052–2060; 1991.

Journal

The FASEB journal – Wiley

Published: Apr 1, 1991

Keywords: ; ; ; ; ; ;

There are no references for this article.