Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta

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 inCOL1A1andCOL1A2that encode for the alpha 1 and alpha 2 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 inCOL1A1and 45 mutations inCOL1A2were 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 inCOL1A1and G337S inCOL1A2were the most frequent (3.52%, 2.11% and 8.89%, respectively), which seem to be hotspot mutations in theCOL1A1andCOL1A2genes in Chinese patients. Conclusions This study describes the mutations in the main pathogenic genes,COL1A1andCOL1A2, 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.

Automated summary

This study analyzed mutations in main pathogenic genes, COL1A1 and COL1A2, and clinical characteristics of osteogenesis imperfecta in China. The study found that there were more sporadic cases than familial cases, and most patients presented with a history of fractures. Hotspot mutations G767S, D1219N in COL1A1 and G337S in COL1A2 were identified as frequent mutations in Chinese patients.