Osteogenesis imperfecta (OI) is a heritable disorder characterized by increased bone fragility, low bone mass, dentinogenesis imperfecta, and blue sclerae. Most patients with OI have a mutation in either COL1A1 or COL1A2, which encode type I collagen. We screened these genes in Japanese patients with OI and compared their genotype and phenotype, focusing on the clinical response to treatment with pamidronate. Sequencing analysis of the genes in 19 families revealed 15 mutations, of which ten were missense mutations, thee were nonsense mutations, and two were frameshift mutations. Each of the 15 mutations was found in unrelated families, even though the patients were from a contiguous region surrounding our hospital. Substitutions of serine for glycine were the commonest mutation in both genes; notably, dentinogenesis imperfecta and fractures at birth were detected with higher frequencies in patients with this substitution when compared with other genotypes. The Z score of the bone mineral density of patients with this substitution was also lower than that of patients with other genotypes. Pamidronate treatment significantly increased the Z score in all patients, and increases in the Z score did not correlate with the OI types, causative genes, or genotype. In conclusion, the efficacy of pamidronate treatment does not seem to be related to the genotype of type I collagen in patients with OI.
Keywords: Mutation; Osteogenesis imperfecta; Pamidronate; Type I collagen.