Osteogenesis imperfecta

COUAICOL1A2 Osteogenesis imperfecta, type T(MIM 1566200) Osteoporosis (MIM 166710) Ehlers-Danlos syndrome type VII autosomal dominant (130060)... 

At least four types of osteogenesis imperfecta are recognized the great majority of mutations in all types are in the COLlAl and COf M2 genes. 

Osteogenesis Imperfecta (eg, MIM 166200) Due to a variety of mutations In the COL /Aland COL 1A2 genes affecting the synthesis and structure of type 1 collagen. 

Diseases associated with impaired synthesis of collagen include scurvy, osteogenesis imperfecta, Ehlers-Danlos syndrome (many types), and Menkes disease. 

The molecular causes of a number of heritable diseases of bone (eg, osteogenesis imperfecta) and of cartilage (eg, the chondrodystrophies) are being revealed by the application of recombinant DNA technology. 

In these 500 cases, there were 26 culture failures, an Incidence of about 5% Nine women of this group underwent a second aminocentesls, and successful cultures were obtained The other 17, or 3 4% of the total, did not obtain any results, either because of spontaneous abortions prior to the time a second amniocentesis could be performed (In four) or because the family elected not to proceed There were no Instances of severe or significant fetal Injury, although small linear "scars" were noted on four fetuses Three fetuses had abnormalities which were not related to the procedure Itself, Including spina bifida, osteogenesis Imperfecta, and congenital heart disease ... 

Bonadio, J. and Byers, P.H. (1985) Subtle structural alterations in the chains of type-I procollagen produce osteogenesis imperfecta type-II. Nature 316, 363-366. 

Osteogenesis imperfecta Mutations in collagen genes Skeletal deformities Fractures, blue sclera... 

In assessing a patient with osteogenesis imperfecta, a history of bone fractures, as well as blue sclerae, are noted. These findings are an example of... 

Allelic heterogeneity is observed in osteogenesis imperfecta (choice A), but allelic heterogeneity causes variable expression in patients and is not the principle described here. 

Osteogenesis imperfecta is a good example of a disease in which locus heterogeneity (choice C) is observed, but this principle refers to the fact that a mutation in either the type 1 procollagen gene on chromosome 7 or the type 1 procoUagen gene on chromosome 17 can result in imperfect formation of the trimeric protein. This principle does not explain the co-occurrence of ftactures and blue sclerae. 

Brittle bone disease, or osteogenesis imperfecta (01), is caused by mutations or absence of one of the genes encoding type I collagen chains, which interferes with assembly and function of the triple helix. 

Dominant negative effect, when the mutant protein interferes with function of the normal protein Osteogenesis imperfecta and the collagen 1A gene (COLIAI) Marfan syndrome and the fibrillin-1 gene (FBNI)... 

Horwitz, E. M., Gordon, P. L., Koo, W. K., et al. (2002), Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta Implications for cells therapy of bone, Proc. Natl. Acad. Sci. USA, 99(13), 8932-8937. 

Eastoe, J. E., Martens, P., Thomas, N. R. The amino acid composition of human hard tissue collagens in osteogenesis imperfecta and dentinogenesis imperfecta. Calc. Tiss. Res. 12, 91 (1973)... 

Lethal form of osteogenesis imperfecta in which the fractures appear in utero. as revealed by this radiograph of a stillborn fetus. 

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