[Corrigendum] Clinical characteristics and the identification of novel mutations of COL1A1 and COL1A2 in 61 Chinese patients with osteogenesis imperfecta.
The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro alpha 1 (I) chain of type I procollagen.
It has been known for three decades that the majority of individuals with OI have mutations in COL1A1 or COL1A2, the two genes coding for collagen type I alpha chains, but in the past 10 years defects in at least 17 other genes have been linked to OI.
The results suggest that mutations in the type I procollagen genes that result in osteogenesis imperfecta can be associated with increased expression of the genes for type IV procollagen.
Substitution of serine for alpha 1(I)-glycine 844 in a severe variant of osteogenesis imperfecta minimally destabilizes the triple helix of type I procollagen. The effects of glycine substitutions on thermal stability are either position of amino acid specific.
Determination of a new collagen type I alpha 2 gene point mutation which causes a Gly640 Cys substitution in osteogenesis imperfecta and prenatal diagnosis by DNA hybridisation.
Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that in the majority of cases is caused by mutations in COL1A1 or COL1A2, the genes that encode the two collagen type I alpha chains, alpha1(I) and alpha2(I).
The majority of Osteogenesis Imperfecta (OI) cases are caused by mutations in one of the two genes, COL1A1 and COL1A2 encoding for the two chains that trimerize to form the procollagen 1 molecule.
Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure.
Substitutions of aspartic acid for glycine-220 and of arginine for glycine-664 in the triple helix of the pro alpha 1(I) chain of type I procollagen produce lethal osteogenesis imperfecta and disrupt the ability of collagen fibrils to incorporate crystalline hydroxyapatite.
Previous observations demonstrated that a lethal variant of osteogenesis imperfecta had two altered alleles for pro alpha 2(I) chains of type I procollagen.
Failure of COL1A1/COL1A2 mutation screening may be due, in a few cases, to further clinical heterogeneity, i.e. additional non-collagenous disease loci are presumably involved in OI types beyond the traditional Sillence's classification.
Osteogenesis imperfecta (OI), or brittle bone disease, is most often caused by dominant mutations in the collagen I genes COL1A1/COL1A2, whereas rarer recessive OI is often caused by mutations in genes encoding collagen I-interacting proteins.
A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cysteine for glycine 904 of the alpha 1(I) chain of type I procollagen. The asymptomatic mother has an unidentified mutation producing an overmodified and unstable type I procollagen.