Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen.We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen.
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.
Thermal stability of type I collagen molecules containing the substitution was decreased, but to a lesser extent than for a nonlethal cysteine for glycine substitution at residue 259 of alpha 2(I), indicating that this measure of molecular stability may be of limited use in explaining the pathogenesis of osteogenesis imperfecta.
A child with a moderately severe form of osteogenesis imperfecta was heterozygous for a G to T transition that resulted in a substitution of cysteine for glycine at position 259 in the COL1A2 gene.
Haplotype analysis of the COL1A2 gene revealed that four probands from five independent OI probands with c.982G>A (p.Gly328Ser) had a common haplotype.
We report two sibs with severe, progressively deforming osteogenesis imperfecta (OI) and homozygosity by descent for a glycine 751 to serine substitution in the alpha2(I) collagen chain due to a G to A transition in the COL1A2 gene.
Three unrelated individuals with perinatally lethal osteogenesis imperfecta resulting from identical Gly502Ser substitutions in the alpha 2-chain of type I collagen.
Mild dominant osteogenesis imperfecta with intrafamilial variability: the cause is a serine for glycine alpha 1(I) 901 substitution in a type-I collagen gene.