Genotype-Phenotype Relationship and Follow-up Analysis of a Chinese Cohort With Osteogenesis Imperfecta

Objective: To evaluate the genotype-phenotype relationship and the effect of treatment on the clinical course of osteogenesis imperfecta (OI).Methods: We established a Chinese hospitalized cohort with OI and followed them up for an average of 6 years. All patients were confirmed as having OI using whole-exome sequencing. We analyzed the genotype -phenotype relationship based on different types, pathogenic mechanisms, and gene inheritance patterns of OI. Additionally, we assessed whether there was a difference in treatment efficacy based on genotype.Results: One hundred sixteen mutations in 6 pathogenic genes (COL1A1, COL1A2, IFITM5, SERPINF1, FKBP10, and WNT1) were identified in 116 patients with type I, III, IV, V, VI, XI, or XV OI. Compared with patients with COL1A1 mutations, patients with COL1A2 mutations were younger at the time of the first fracture, whereas other phenotypes were similar. When 3 groups (helical, haploinsufficiency, and non -collagen I gene mutations) were compared, patients with helical mutations were the shortest and most prone to dentinogenesis imperfecta. Patients with haploinsufficiency mutations were the oldest at the time of the first fracture. Moreover, patients with non-collagen I gene mutations were least sus-ceptible to blue sclerae and had the highest fracture frequency. Furthermore, there were some minor phenotypic differences among non-collagen I gene mutations. Interestingly, pamidronate achieved excellent results in the treatment of patients with OI, and the treatment effect appeared to be unrelated to their genotypes.Conclusion: Our findings indicated a genotype-phenotype relationship and a similar effect of pamidro-nate treatment in patients with OI, which could provide a basis for guiding clinical treatment and pre-dicting OI prognosis.(c) 2022 AACE. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

The study aimed to evaluate the relationship between genotype and phenotype in osteogenesis imperfecta (OI) and the effect of treatment on the disease course. The research identified genotype-phenotype associations based on different types, pathogenic mechanisms, and gene inheritance patterns of OI in a Chinese cohort. Pamidronate treatment demonstrated excellent results regardless of genotype.