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

Autor: Zhytnik L; Department of Traumatology and Orthopedics, University of Tartu, Tartu, Estonia., Maasalu K; Department of Traumatology and Orthopedics, University of Tartu, Tartu, Estonia.; Clinic of Traumatology and Orthopedics, Tartu University Hospital, Tartu, Estonia., Duy BH; Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam., Pashenko A; Department of Pediatric Orthopedics, Sytenko Institute of Spine and Joint Pathology, AMS Ukraine, Kharkiv, Ukraine., Khmyzov S; Department of Pediatric Orthopedics, Sytenko Institute of Spine and Joint Pathology, AMS Ukraine, Kharkiv, Ukraine., Reimann E; Centre of Translational Medicine, University of Tartu, Tartu, Estonia.; Department of Pathophysiology, University of Tartu, Tartu, Estonia., Prans E; Department of Pathophysiology, University of Tartu, Tartu, Estonia., Kõks S; Centre for Comparative Genomics, Murdoch University, Perth, Australia.; Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, Australia., Märtson A; Department of Traumatology and Orthopedics, University of Tartu, Tartu, Estonia.; Clinic of Traumatology and Orthopedics, Tartu University Hospital, Tartu, Estonia.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2019 Mar; Vol. 7 (3), pp. e559. Date of Electronic Publication: 2019 Jan 24.
DOI: 10.1002/mgg3.559
Abstrakt: 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.
(© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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