Genotype-phenotype relationship and follow-up analysis of a Chinese osteogenesis imperfecta cohort

Endocr Pract. 2022 May 9:S1530-891X(22)00501-8. doi: 10.1016/j.eprac.2022.05.003. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluating the genotype-phenotype relationship and the effect of treatment on the clinical course of Osteogenesis imperfecta (OI).

METHODS: We established a Chinese hospitalized OI cohort and followed up for an average of 6 years. All the patients were confirmed by Whole-exome sequencing. We analyzed the genotype-phenotype relationship based on the different types, pathogenic mechanisms, and gene inheritance patterns. Additionally, we assessed if there was a difference in treatment efficacy by genotype.

RESULTS: The 116 mutations in 6 pathogenic genes (COL1A1, COL1A2, IFITM5, SERPINF1, FKBP10, and WNT1) were identified in 116 patients with OI type I, III, IV, V, VI, XI or XV. Compared to patients with COL1A1 mutations, patients with COL1A2 mutations had a younger age at first fracture, whereas other phenotypes were similar. Comparing the three groups (helical, haploinsufficiency, non-collagen I gene mutations), patients with helical mutations were the shortest and the most prone to DI. Patients with haploinsufficiency mutations exhibited the oldest age at first fracture. Moreover, patients with non-collagen I gene mutations were least susceptible to blue sclerae and had the highest fracture frequency. Furthermore, there were some minor phenotypic differences between non-collagen I gene mutations. Interestingly, pamidronate achieved excellent results in the treatment of OI patients, and the treatment effect appeared to be unrelated to genotypes.

CONCLUSION: Our findings indicate a genotype-phenotype relationship and similar pamidronate treatment effect in OI patients, which could provide a basis for guiding clinical treatment and predicting OI prognosis.

PMID:35550181 | DOI:10.1016/j.eprac.2022.05.003