Introduction: Osteogenesis imperfecta (OI) is a well-known heritable disorder of connective tissue characterized by skeletal fragility and low bone mass. Nearly 90% of patients with OI have disease variants in COL1A1 and COL1A2 that encode for the α1 and α2 chains of type I collagen.
Materials and methods: A retrospective analysis of 185 probands who were diagnosed with OI in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from March 2005 to December 2019 was performed.
Results: A total of 140 mutations in COL1A1 and 45 mutations in COL1A2 were identified, of which 18 variations were novel. In the phenotype analysis, there were more sporadic cases than familial OI cases in China (54.6% vs. 45.4%, P < 0.001). A total of 98.9% of patients presented with a fracture history. The most common fracture sites were extremity long bones (femur, tibia-fibula and radius-ulna accounted for 36.6%, 17.1% and 11.7%, respectively). Patients with OI types III and IV, especially type III, had a higher proportion of dentinogenesis imperfecta (DI) than patients with OI type I (55% vs. 28%, P < 0.001). Interestingly, G767S and D1219N in COL1A1 and G337S in COL1A2 were the most frequent (3.52%, 2.11% and 8.89%, respectively), which seem to be hotspot mutations in the COL1A1 and COL1A2 genes in Chinese patients.
Conclusions: This study describes the mutations in the main pathogenic genes, COL1A1 and COL1A2, and the clinical characteristics of osteogenesis imperfecta in China. Furthermore, these findings help reveal the genetic basis of Asian OI patients and contribute to genetic counselling.
Keywords: COL1A1; COL1A2; Genotype; Osteogenesis imperfecta; Phenotype.