We preformed linkage analyses in eight OI type III families using RFLPs associated with the COL1A1 and COL1A2 loci to determine whether mutations in the genes for type I collagen were responsible for this form of OI.
Direct sequencing of PCR products derived from cDNAs for the pro alpha 1 and pro alpha 2 chains of type I procollagen as a screening method to detect mutations in patients with osteogenesis imperfecta.
Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III.
Mutation in the carboxy-terminal propeptide of the Pro alpha 1(I) chain of type I collagen in a child with severe osteogenesis imperfecta (OI type III): possible implications for protein folding.
Arachnoid cyst and chronic subdural haematoma in a child with osteogenesis imperfecta type III resulting from the substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen.
A Gly859Ser substitution in the triple helical domain of the alpha 2 chain of type I collagen resulting in osteogenesis imperfecta type III in two unrelated individuals.
The effects of different cysteine for glycine substitutions within alpha 2(I) chains. Evidence of distinct structural domains within the type I collagen triple helix.
Because of (i) absence of COL1A1/2 mutations, (ii) a consanguineous pedigree with a similarly affected sibling and (iii) the existence of congenital joint contractures with absence of recessive variants in PLOD2, mutation analysis was performed of the FKBP10 gene, recently associated with Bruck syndrome and/or recessive OI.
Biallelic loss-of-function mutations in WNT1 result in a recessive clinical picture that includes bone fragility with a moderately severe and progressive presentation that is not easily distinguished from dominant OI type III.
Our study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset.