Collagen osteogenesis imperfecta

The diseases and disorders chosen for discussion and the order of presentation parallel subject matter taught in most first-year medical biochemistry. Chapters in the first part of the book, Nucleic Acids and Protein Structure, illustrate the relationships of protein structure and function with respect to collagen (Osteogenesis Imperfecta) and hemoglobin (Sickle Cell Anemia). The chapters Fragile X Syndrome and Hereditary Spherocytosis discuss key aspects of DNA and protein structure and their respective role in chromosomal and cytoskeletal structure. The chapter cardiac troponin and myocardial infarction provides an up-to-date demonstration of the usefulness of both structural proteins and enzymes as markers of cardiovascular disease, while the chapter cx Anti trypsin Deficiency discusses the important role of endogenous enzyme inhibitors. 

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. 

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

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)... 

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)... 

Collagen abnormalities, such as Ehlers-Damlos syndrome. Marfan s syndrome, pseudoxanthoma elasticum. and osteogenesis imperfecta... 

There are conflicting reports on a possible increased risk of fractures in children with osteogenesis imperfecta treated with somatropin, many of whom have a qualitative defect in collagen (77,78). 

Antoniazzi F, Bertoldo F, Mottes M, Valli M, Sirpresi S, Zamboni G, Valentini R, Tato L. Growth hormone treatment in osteogenesis imperfecta with quantitative defect of type I collagen synthesis. J Pediatr 1996 129(3) 432-9. 

Beck, K., Chan, V. C., Shenoy, N., Kirkpatrick, A., Ramshaw, J. A., and Brodsky, B. (2000). Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine. Proc. Natl. Acad. Sci. 97, 4273-4278. 

Marini, J. C., Lewis, M. B., Wang, Q., Chen, K. J., and Orrison, B. M. (1993). Serine for glycine substitutions in type I collagen in two cases of type IV osteogenesis imperfecta (OI). Additional evidence for a regional model of OI pathophysiology. J Biol. Chem. 268, 2667-2673. 

Radmer, R. J., and Klein, T. E. (2004). Severity of osteogenesis imperfecta and structure of a collagen-like peptide modeling a lethal mutation site. Biochemistry 43, 5314—5323. 

Kozloff and coworkers reported changes in mineralization for the Brtl mouse, a model of Sillence type IV osteogenesis imperfecta in which glycine-349 is replaced by cysteine in one or both a. chains of matrix collagen [43]. They found no differences in crystallinity (inverse band width of phosphate Vi between wild type and the heterozygous brtl mouse). Mineral/matrix ratios were different. 

Bachinger HP, Morris NP, Davis JM Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen., 1/ / J Med Genet 45 152-162,1993. 

Kuznetsova NV Forlino A, Cabral WA, et al. Structure, stability and interactions of type I collagen with GLY349-CYS substitution in a 1(1)chain in a murine osteogenesis imperfecta model. Matrix Biol 2 x101-112,2001. 

Schwatze U, Starman BJ, Byers PH (1999) Redefinition of exon 7 in the COLlAl gene of type I collagen by an intron 8 spUce-donor-site mutation in a form of osteogenesis imperfecta influence of intron splice order on outcome of splice-site mutation. Am J Hum Genet 65 336-344... 

In osteogenesis imperfecta, the child has brittle bones , which fracture easily. There may also be blue sclerae, hearing defects, and dental abnormalities. There are a variety of forms of this condition that involve defects in the structure of collagen. 

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