Clinical and genetic characteristics of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a genetically heterogeneous group of disorders characterized by reduced bone mineral density, resulting in increased bone fragility and pathological fractures. Advanced molecular genetic diagnostic methods now enable precise identification of genetic variants and specific OI forms, thereby optimizing clinical management and diagnostic strategies. The objective of this study was to analyze clinical and genetic characteristics of monogenic isolated and syndromic forms of OI to enhance their differential diagnosis. A total of 423 patients from 290 unrelated families were examined using clinical-genealogical assessment and comprehensive molecular genetic techniques, including targeted sequencing, exome sequencing, genome sequencing, and Sanger sequencing. An etiological factor was successfully identified in 94.7% of the patients, with 202 nucleotide variants detected across 11 genes; notably, 80 variants were novel. Autosomal dominant forms of OI associated with mutations in the COL1A1 and COL1A2 genes comprised 83.3% of the entire cohort. The study determined the prevalence and detailed clinical-radiological features of rare genetic variants linked to the IFITM5, SERPINF1, P3H1, FKBP10, and BMP1 genes. Furthermore, recurrent nucleotide variants were identified in the IFITM5, SERPINF1, SGMS2, and FKBP10 genes. The findings have allowed the refinement of clinical and molecular genetic diagnostic approaches, significantly contributing to improved genetic counseling and clinical management of patients with various forms of OI.

1. Forlino A., Marini J.C. Osteogenesis imperfecta. Lancet. 2016;387(10028):1657-1671.

2. Marini J..C, Forlino A., Bächinger H.P. et al. Osteogenesis imperfecta. Nature Reviews Disease Primers. 2017;3:17052.

3. Unger S., Ferreira C.R., Mortier G.R. et al. Nosology of genetic skeletal disorders: 2023 revision. American Journal of Medical Genetics Part A. 2023;191(5):1164-1209.