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

Lidiia Zhytnik, Katre Maasalu, Binh Ho Duy, Andrey Pashenko, Sergey Khmyzov, Ene Reimann, Ele Prans, Sulev Koks, Aare Martson

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number559
Number of pages11
JournalMolecular genetics & genomic medicine
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 2019

Cite this

Zhytnik, L., Maasalu, K., Binh Ho Duy, Pashenko, A., Khmyzov, S., Reimann, E., ... Martson, A. (2019). De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta. Molecular genetics & genomic medicine, 7(3), [559]. https://doi.org/10.1002/mgg3.559
Zhytnik, Lidiia ; Maasalu, Katre ; Binh Ho Duy ; Pashenko, Andrey ; Khmyzov, Sergey ; Reimann, Ene ; Prans, Ele ; Koks, Sulev ; Martson, Aare. / De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta. In: Molecular genetics & genomic medicine. 2019 ; Vol. 7, No. 3.
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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. ResultsResults 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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Zhytnik, L, Maasalu, K, Binh Ho Duy, Pashenko, A, Khmyzov, S, Reimann, E, Prans, E, Koks, S & Martson, A 2019, 'De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta' Molecular genetics & genomic medicine, vol. 7, no. 3, 559. https://doi.org/10.1002/mgg3.559

De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta. / Zhytnik, Lidiia; Maasalu, Katre; Binh Ho Duy; Pashenko, Andrey; Khmyzov, Sergey; Reimann, Ene; Prans, Ele; Koks, Sulev; Martson, Aare.

In: Molecular genetics & genomic medicine, Vol. 7, No. 3, 559, 03.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta

AU - Zhytnik, Lidiia

AU - Maasalu, Katre

AU - Binh Ho Duy, null

AU - Pashenko, Andrey

AU - Khmyzov, Sergey

AU - Reimann, Ene

AU - Prans, Ele

AU - Koks, Sulev

AU - Martson, Aare

PY - 2019/3

Y1 - 2019/3

N2 - 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. ResultsResults 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.

AB - 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. ResultsResults 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.

KW - bone fragility

KW - collagen

KW - de novo

KW - osteogenesis imperfecta

KW - Sanger sequencing

KW - COL1A1 GENE

KW - I COLLAGEN

KW - MUTATIONS

U2 - 10.1002/mgg3.559

DO - 10.1002/mgg3.559

M3 - Article

VL - 7

JO - Molecular Genetics and Genomic Medicine

JF - Molecular Genetics and Genomic Medicine

SN - 2324-9269

IS - 3

M1 - 559

ER -