Substitution of an aspartic acid for glycine 700 in the alpha 2(I) chain of type I collagen in a recurrent lethal type II osteogenesis imperfecta dramatically affects the mineralization of bone.

摘要: We describe a new dominant mutation of type I collagen responsible for recurrent lethal osteogenesis imperfecta. Dermal cultured fibroblasts the proband produced both normal and overmodified chains. Previous results (Cohen-Solal, L., Bonaventure, J., Maroteaux, P. (1991) Hum. Genet. 87, 297-301) cyanogen bromide peptide mapping after non-equilibrium pH gradient gel electrophoresis indicated that anomaly was charge localized in alpha 2CB3-5A. The identified as G to A transition COL1A2 gene, which converts glycine 700 aspartic acid 2I chain. This caused abolition ScrFI site, also absent suspected mosaic father. Pulse-chase experiment showed intracellular retention increase degradation synthesized collagen. To understand more directly tissue defect imperfecta, skin especially bone were studied with biochemical transmission electron microscopy techniques. Collagen matrix tissues dramatically decreased presented retarded migration, showing abnormal molecules incorporated during fibrillogenesis. mostly remained within osteoblasts, typical features retention. observed presence spheritic aggregates mineral, unrelated scarce thin fibrils, bone. Such mineralization could be consequence not only decrease content but importantly inability form an organized network necessary deposition apatite crystallites.