Osteogenesis imperfecta: Biochemical and clinical evaluation of 13 cases

Abstract

Skin fibroblasts were cultured from 13 patients with Osteogenesis imperfecta and collagen biosynthesis was investigated in vitro. In those patients characterised by only mild manifestations of the disease, the ratio of collagen types I and III was disturbed. By contrast, fibroblasts obtained from patients with Osteogenesis imperfecta of a more severe type synthesised collagen types I/III in a normal ratio.

Type I osteogenesis imperfecta: a nonfunctional allele for pro alpha 1 (I) chains of type I procollagen.

“…This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. tains a decreased ratio of type I to type III collagen (7) and that dermal fibroblasts from affected patients produce a decreased ratio oftype I to type III collagen in culture (5). Analysis ofskin and cell culture medium of01 and control cells confirmed these results and, in addition, demonstrated that the production of total collagenous protein by the OI cells was decreased to about halfof the control levels (Table 2).…”

“…Cultures were matched for passage (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) Other Procedures. Collagenase digestions were performed with purified bacterial collagenase (Advance Biofactures, Lynnbrook, NY) by using standard methods (12).…”

“…There are many examples ofmutations that alter the expression ofa single gene product, but mutations in regulatory genes that control more than one transcriptional unit are rare (1,2). In type I osteogenesis imperfecta (01), a dominantly inherited disease that presents clinically with bone fragility, blue sclerae, and presenile hearing loss (3,4), the production of type I collagen by cultured cells (5) and the content of type I collagen in skin (6,7) and bone (8) is decreased by =50%. Because type I procollagen contains proal(I) and proa2(I) chains that are coded for by separate mRNA molecules (9), the primary defect in type I OI may involve a regulatory gene that controls the synthesis of proal(I) and proa2(I) chains coordinately.…”

Molecular and clinical aspects of connective tissue

“…In patients with 01, mainly defects of type I collagen have been identified. Thus, reduced synthesis of type I, leading to a relative increase of type III collagen has been reported [57][58][59] and the collagen chains have been found to be over-hydroxylated [60][61][62], which was accompanied by an increased content of glucosyl and galactosyl residues. In addition, some patients were characterized by a high degradation of collagen and by the formation of IXI (I) trimers lacking the 1X2(I) chain [63].…”

Molecular Defects in Inborn Disorders of Collagen Metabolism

“…An increased type Ill/type I collagen ratio has been described in patients with mild, severe and lethal OI by several authors [64][65][66][67], One of these cell lines, derived from a patient with a mild type of OI, also failed to synthesize the a2-chain of type I collagen in a previous re port [68], The same defect, namely the ab sence of the a2-chain in type I collagen, has since then been described in another cell line derived from a patient with moderate OI [69]. Increased hyaluronic acid synthesis by skin fibroblasts derived from patients with OI has also been reported [70].…”