The heritable diseases of connective tissue are caused by known or putative defects in the synthesis of collagens, proteoglycans, glycoproteins, or attachment proteins of the extracellular matrix. Abnormal synthesis of type I collagen has been reported in several clinical variants of osteogenesis imperfecta. Because clinical classification of these variants is limited by genetic heterogeneity and variable expression, biochemical criteria should be used for precise definition of the variants. Newly recognized molecular defects in osteogenesis imperfecta include the diminished formation of type I collagen and alpha-1[I] messenger RNA; abnormal synthesis or faulty assembly of alpha-2[I]; deletion or insertion of base pairs in the gene for alpha-1[I] or alpha-2[I] and failure to secrete type I procollagen; and substitution of cysteine for glycine in the triple helix. These molecular defects are characteristic of several variants. However, the molecular lesion in most cases of severe osteogenesis imperfecta has not been identified; synthesis of type I collagen and alpha-1:alpha-2 chain ratios appears to be normal. Production of an alpha-1 trimer may represent one such lesion in severe disease.
ASJC Scopus subject areas
- Internal Medicine