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. 2019 Mar;7(3):e559.
doi: 10.1002/mgg3.559. Epub 2019 Jan 24.

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

Affiliations

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

Lidiia Zhytnik et al. Mol Genet Genomic Med. 2019 Mar.

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.

Keywords: Sanger sequencing; bone fragility; collagen; de novo; osteogenesis imperfecta.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Pedigree trees, photographs, and genotypes of Vietnamese patients with familial (a) and de novo (b) osteogenesis imperfecta. 1 COL1A1 GenBank reference sequence (gDNA NG_007400.1, cDNA NM_000088.3)
Figure 2
Figure 2
Proportion (%) of de novo mutations by population
Figure 3
Figure 3
(a) Distribution of osteogenesis imperfecta (OI) types in collagen type I de novo and inherited OI. (b) Distribution of OI types in subjects with de novo or inherited OI
Figure 4
Figure 4
(a) Distribution of COL1A1 1 and COL1A2 2 mutations for de novo and inherited osteogenesis imperfecta (OI). (b) Functional types of mutations in de novo and inherited OI. (c) Collagen defect distributions in de novo and inherited OI. 1 COL1A1 GenBank reference sequence (gDNA NG_007400.1, cDNA NM_000088.3). 2 COL1A2 GenBank reference sequence (gDNA NG_007405.1, cDNA NM_000089.3)

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References

    1. Acuna‐Hidalgo, R. , Veltman, J. A. , & Hoischen, A. (2016). New insights into the generation and role of de novo mutations in health and disease. Genome Biology, 17, 241 10.1186/s13059-016-1110-1 - DOI - PMC - PubMed
    1. Ben Amor, I. M. , Glorieux, F. H. , & Rauch, F. (2011). Genotype‐phenotype correlations in autosomal dominant osteogenesis imperfecta. Journal of Osteoporosis, 2011, 540178. - PMC - PubMed
    1. Binh, H. D. , Maasalu, K. , Dung, V. C. , Ngoc, C. T. B. , Hung, T. T. , Nam, T. V. , … Märtson, A. (2017). The clinical features of osteogenesis imperfecta in Vietnam. International Orthopaedics, 41, 21–29. 10.1007/s00264-016-3315-z - DOI - PubMed
    1. Bonod-Bidaud, C. , & Ruggiero, F. (2013). Inherited connective tissue disorders of collagens: Lessons from targeted mutagenesis In David Figurski (Ed), genetic manipulation of DNA and protein. London: IntechOpen.
    1. Byers, P. H. , & Steiner, R. D. (1992). Osteogenesis imperfecta. Annual Review of Medicine, 43, 269–282. 10.1146/annurev.me.43.020192.001413 - DOI - PubMed

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