De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta
- PMID: 30675999
- PMCID: PMC6418448
- DOI: 10.1002/mgg3.559
De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta
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.
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Conflict of interest statement
None declared.
Figures
Similar articles
-
Comparing Clinical and Genetic Characteristics of De Novo and Inherited COL1A1/COL1A2 Variants in a Large Chinese Cohort of Osteogenesis Imperfecta.Front Endocrinol (Lausanne). 2022 Jul 14;13:935905. doi: 10.3389/fendo.2022.935905. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 35909573 Free PMC article.
-
Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta.Hum Genomics. 2016 Aug 12;10(1):27. doi: 10.1186/s40246-016-0083-1. Hum Genomics. 2016. PMID: 27519266 Free PMC article.
-
IFITM5 pathogenic variant causes osteogenesis imperfecta V with various phenotype severity in Ukrainian and Vietnamese patients.Hum Genomics. 2019 Jun 3;13(1):25. doi: 10.1186/s40246-019-0209-3. Hum Genomics. 2019. PMID: 31159867 Free PMC article.
-
[Genetic basis for skeletal disease. Osteogenesis imperfecta and genetic abnormalities].Clin Calcium. 2010 Aug;20(8):1190-5. Clin Calcium. 2010. PMID: 20675929 Review. Japanese.
-
Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans.Acta Biochim Pol. 2002;49(2):433-41. Acta Biochim Pol. 2002. PMID: 12362985 Review.
Cited by
-
A De novo Mutation in the COL1A1 Gene Leading to Severe Osteogenesis Imperfecta: Case Report and Review of the Literature.AJP Rep. 2024 Sep 12;14(3):e215-e223. doi: 10.1055/a-2388-3190. eCollection 2024 Jul. AJP Rep. 2024. PMID: 39268228 Free PMC article.
-
Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients.Curr Issues Mol Biol. 2024 Apr 29;46(5):4106-4118. doi: 10.3390/cimb46050252. Curr Issues Mol Biol. 2024. PMID: 38785520 Free PMC article.
-
Case Report: A novel de novo variant of COL1A1 in fetal genetic osteogenesis imperfecta.Front Endocrinol (Lausanne). 2023 Nov 2;14:1267252. doi: 10.3389/fendo.2023.1267252. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 38027129 Free PMC article.
-
Classification of osteogenesis imperfecta: Importance for prophylaxis and genetic counseling.World J Clin Cases. 2023 Apr 26;11(12):2604-2620. doi: 10.12998/wjcc.v11.i12.2604. World J Clin Cases. 2023. PMID: 37214584 Free PMC article. Review.
-
Prevalence of Monogenic Bone Disorders in a Dutch Cohort of Atypical Femur Fracture Patients.J Bone Miner Res. 2023 Jun;38(6):896-906. doi: 10.1002/jbmr.4801. Epub 2023 Apr 19. J Bone Miner Res. 2023. PMID: 37076969 Free PMC article.
References
-
- 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.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous
