De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley Periodicals, Inc.
Abstract
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 per formed with Sanger sequencing.
Results: Results showed that 56.16% of the OI cases were caused by de novo patho genic 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 pro mote the further understanding of OI etiology, and assist with diagnostics proce dures, as well as with family plannin
Description
Keywords
bone fragility, collagen, de novo, osteogenesis imperfecta, Sanger sequencing