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De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta
Journal article   Open access   Peer reviewed

De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta

L. Zhytnik, K. Maasalu, B.H. Duy, A. Pashenko, S. Khmyzov, E. Reimann, E. Prans, S. Kõks and A. Märtson
Molecular Genetics & Genomic Medicine, Vol.7(3), e559
2019
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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 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.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.132 Extracellular Matrix & Cell Differentiation
1.132.1065 Collagen Disorders
Web Of Science research areas
Genetics & Heredity
ESI research areas
Molecular Biology & Genetics
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