Background
Osteogenesis imperfecta (OI) is a rare genetic bone fragility disorder. In the current study, differences between the genotypes and phenotypes of
de novo
and inherited collagen‐related OI were investigated.
Methods
A comparative analysis was performed of the genotypes and phenotypes of 146 unrelated inherited and
de novo
collagen I OI cases from Estonia, Ukraine, and Vietnam. Mutational analysis of the subjects and all available parents were performed with Sanger sequencing.
Results
Results showed that 56.16% of the OI cases were caused by
de novo
pathogenic variants. The proportion of OI types OI1, OI4, and OI3 among subjects with inherited OI was 45.31%, 46.88%, and 7.81%, respectively. Among subjects with
de novo
OI, the proportions of OI types (OI1, OI4, and OI3) were almost equal. Both inherited and
de novo
OI pathogenic variants occurred more often in the
COL1A1
gene than in the
COL1A2
. The majority of
de novo
cases were missense pathogenic variants, whereas inherited OI was mostly caused by loss of function pathogenic variants.
Conclusion
In summary, there were significant differences between the phenotypes and genotypes of subjects with
de novo
and inherited OI. These findings may promote the further understanding of OI etiology, and assist with diagnostics procedures, as well as with family planning.