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Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta
Osteogenesis imperfecta (OI) is a rare genetic disorder also known as a “brittle bone disease.” Around 90% of patients with OI harbor loss‐of‐function or dominant negative pathogenic variants in the COL1A1 and COL1A2 genes, which code for collagen type I α1 and α2 chains. Collagen‐related forms of t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485955/ https://www.ncbi.nlm.nih.gov/pubmed/32166892 http://dx.doi.org/10.1111/cts.12783 |
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author | Zhytnik, Lidiia Maasalu, Katre Reimand, Tiia Duy, Binh Ho Kõks, Sulev Märtson, Aare |
author_facet | Zhytnik, Lidiia Maasalu, Katre Reimand, Tiia Duy, Binh Ho Kõks, Sulev Märtson, Aare |
author_sort | Zhytnik, Lidiia |
collection | PubMed |
description | Osteogenesis imperfecta (OI) is a rare genetic disorder also known as a “brittle bone disease.” Around 90% of patients with OI harbor loss‐of‐function or dominant negative pathogenic variants in the COL1A1 and COL1A2 genes, which code for collagen type I α1 and α2 chains. Collagen‐related forms of the disorder are classified as Sillence OI types I–IV. OI phenotype expression ranges from mild to lethal. The current study aims to evaluate associations between interfamilial and intrafamilial phenotypic variability and genotype characteristics of patients with collagen‐related OI. The study was based on a systematic review of collagen‐related OI cases from the University of Tartu OI database (n = 137 individuals from 81 families) and the Dalgleish database (n = 479 individuals). Interfamilial variability analysis has shown that 17.74% of all studied OI‐related variants were associated with the same phenotype. The remaining 82.26% of pathogenic variants were associated with variable phenotypes. Additionally, higher interfamilial variability correlated with the COL1A1 gene (P value = 0.001) and dominant‐negative variants (P value = 0.0007). Within intrafamilial variability, 32.81% families had increasing or decreasing OI phenotype severity across generations. Higher intrafamilial variability of phenotypes correlated with the collagen I dominant negative variants (P value = 0.0246). The current study shows that, in line with other phenotype modification factors, OI interfamilial and intrafamilial diversity potential is associated with the genotype characteristics of the OI‐causing pathogenic variants. The results of the current study may advance knowledge of OI phenotype modification as well as assist family planning and the evaluation of disease progression in subsequent generations. |
format | Online Article Text |
id | pubmed-7485955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74859552020-09-18 Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta Zhytnik, Lidiia Maasalu, Katre Reimand, Tiia Duy, Binh Ho Kõks, Sulev Märtson, Aare Clin Transl Sci Research Osteogenesis imperfecta (OI) is a rare genetic disorder also known as a “brittle bone disease.” Around 90% of patients with OI harbor loss‐of‐function or dominant negative pathogenic variants in the COL1A1 and COL1A2 genes, which code for collagen type I α1 and α2 chains. Collagen‐related forms of the disorder are classified as Sillence OI types I–IV. OI phenotype expression ranges from mild to lethal. The current study aims to evaluate associations between interfamilial and intrafamilial phenotypic variability and genotype characteristics of patients with collagen‐related OI. The study was based on a systematic review of collagen‐related OI cases from the University of Tartu OI database (n = 137 individuals from 81 families) and the Dalgleish database (n = 479 individuals). Interfamilial variability analysis has shown that 17.74% of all studied OI‐related variants were associated with the same phenotype. The remaining 82.26% of pathogenic variants were associated with variable phenotypes. Additionally, higher interfamilial variability correlated with the COL1A1 gene (P value = 0.001) and dominant‐negative variants (P value = 0.0007). Within intrafamilial variability, 32.81% families had increasing or decreasing OI phenotype severity across generations. Higher intrafamilial variability of phenotypes correlated with the collagen I dominant negative variants (P value = 0.0246). The current study shows that, in line with other phenotype modification factors, OI interfamilial and intrafamilial diversity potential is associated with the genotype characteristics of the OI‐causing pathogenic variants. The results of the current study may advance knowledge of OI phenotype modification as well as assist family planning and the evaluation of disease progression in subsequent generations. John Wiley and Sons Inc. 2020-04-03 2020-09 /pmc/articles/PMC7485955/ /pubmed/32166892 http://dx.doi.org/10.1111/cts.12783 Text en © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Zhytnik, Lidiia Maasalu, Katre Reimand, Tiia Duy, Binh Ho Kõks, Sulev Märtson, Aare Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta |
title | Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta |
title_full | Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta |
title_fullStr | Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta |
title_full_unstemmed | Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta |
title_short | Inter‐ and Intrafamilial Phenotypic Variability in Individuals with Collagen‐Related Osteogenesis Imperfecta |
title_sort | inter‐ and intrafamilial phenotypic variability in individuals with collagen‐related osteogenesis imperfecta |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485955/ https://www.ncbi.nlm.nih.gov/pubmed/32166892 http://dx.doi.org/10.1111/cts.12783 |
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