The variety of mutations described in the COL1A1/COL1A2 genes giving rise to an OI phenotype is in accordance with the clinical heterogeneity of the disease.Hum Mutat 17:434, 2001.
The segregation of the two type I collagen structural gene loci COL1A1 and COL1A2 was analysed in eleven osteogenesis imperfecta pedigrees by means of restriction-site variants at, or close to, these loci.
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.
The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral-facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence.
The phenotypic features of osteogenesis imperfecta resulting from a mutation of the carboxyl-terminal pro alpha 1 (I) propeptide that impairs the assembly of type I procollagen and formation of the extracellular matrix.
The mutations p.Gly257Arg, p.Gly767Ser and p.Gly821Ser in COL1A1 and p.Gly337Ser in COL1A2 may be located at a mutation hotspot for human OI due to the high repetition rate in OI patients.
The mRNAs for the pro-alpha 1(I) and pro-alpha 2(I) chains of type I procollagen are translated at the same rate in normal human fibroblasts and in fibroblasts from two variants of osteogenesis imperfecta with altered steady state ratios of the two mRNAs.
The molecular defect in an autosomal dominant form of osteogenesis imperfecta. Synthesis of type I procollagen containing cysteine in the triple-helical domain of pro-alpha 1(I) chains.
The molecular defect in a nonlethal variant of osteogenesis imperfecta. Synthesis of pro-alpha 2(I) chains which are not incorporated into trimers of type I procollagen.
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.
The large majority of individuals with an OI phenotype have disease-causing dominant variants in COL1A1 or COL1A2, the genes coding for collagen type I. Interestingly, large sequencing databases indicate that there are about 10 times more carriers of COL1A1/COL1A2 variants that should lead to OI than there are individuals with a diagnosis of OI.
The efficiency of the new process is shown by confirmation of the identification of the Col1A2 locus in osteogenesis imperfecta patients from Amish families.
The discovery of mutations involving CRTAP and LEPRE1 genes in severe/lethal and recessively inherited osteogenesis imperfecta has provided partial answers to questions about 'other' osteogenesis imperfecta genes in patients with an osteogenesis imperfecta phenotype but no COL1A1 and COL1A2 mutations.
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.
The clinical features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by arginine in the pro alpha 1(I) chain of type I procollagen.
The clinical features of osteogenesis imperfecta resulting from a non-functional carboxy terminal pro alpha 1(I) propeptide of type I procollagen and a severe deficiency of normal type I collagen in tissues.
The absence of bone fragility in our patients indicates that cardiac valvular EDS is also separated from patients with autosomal recessive osteogenesis imperfecta and variants in COL1A2, as well as from individuals with autosomal dominant osteogenesis imperfecta and severe cardiac valvular disease.
The 2017 classification of Ehlers-Danlos syndromes (EDS) identifies three types associated with causative variants in COL1A1/COL1A2 and distinct from osteogenesis imperfecta (OI).
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.
Substitutions for glycine alpha 1-637 and glycine alpha 2-694 of type I procollagen in lethal osteogenesis imperfecta. The conformational strain on the triple helix introduced by a glycine substitution can be transmitted along the helix.