Osteogenesis imperfecta or "brittle bone disease" is a congenital disorder of connective tissue causing the bone to break easily. Around 85-90% of cases are due to autosomal dominant mutations in the genes encoding type I collagen, the major organic component of bone. Genotype-phenotype correlations have shown that quantitative defects of collagen type I lead to mild OI, whereas structural defects show a wide clinical range from mild to perinatal lethal. This may partially be explained by the type of amino acid substitution and the relative location in the domain structure. To fully understand the variability of the clinical manifestation and the underlying pathomechanisms, further investigations are required. In Nov 3, 2017, U. Lindert and others published an article in << Calcified Tissue International >> which title is “ Insight into the Pathology of a COL1A1 Signal Peptide Heterozygous Mutation Leading to Severe Osteogenesis Imperfecta ”. Here they provide the first biochemical characterization of a mutation at the signal peptide cleavage site of COL1A1, a domain not yet characterized. By steady-state analysis, they observed reduced production of collagen type I. Furthermore, by pulse-chase analysis they detected delayed secretion and partial intracellular retention of collagen I. These results further support the hypothesis that mechanisms interfering with ER integrity play an important role in the pathology of severe OI.
Read More
