| Autor: |
J Jacob, Jeffrey Bonadio, R E Gelinas, Karen A. Holbrook, Peter H. Byers |
| Rok vydání: |
1985 |
| Předmět: |
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| Zdroj: |
Scopus-Elsevier |
| ISSN: |
0021-9258 |
| DOI: |
10.1016/s0021-9258(18)89655-7 |
| Popis: |
Cultured dermal fibroblasts from an infant with the lethal perinatal form of osteogenesis imperfecta (type II) synthesize normal and abnormal forms of type I procollagen. The abnormal type I procollagen molecules are excessively modified during their intracellular stay, have a lower than normal melting transition temperature, are secreted at a reduced rate, and form abnormally thin collagen fibrils in the extracellular matrix in vitro. Overmodification of the abnormal type I procollagen molecules was limited to the NH2-terminal three-fourths of the triple helical domain. Two-dimensional mapping of modified and unmodified alpha chains of type I collagen demonstrated neither charge alterations nor large insertions or deletions in the region of alpha 1(I) and alpha 2(I) in which overmodification begins. Both the structure and function of type I procollagen synthesized by cells from the parents of this infant were normal. The simplest interpretation of the results of this study is that the osteogenesis imperfecta phenotype arose from a new dominant mutation in one of the genes encoding the chains of type I procollagen. Given the requirement for glycine in every third position of the triple helical domain, the mutation may represent a single amino acid substitution for a glycine residue. These findings demonstrate further heterogeneity in the biochemical basis of osteogenesis imperfecta type II and suggest that the nature and location of mutations in type I procollagen may determine phenotypic variation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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