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Open Access CC BY-NC V4.0
Journal article
Inter- and Intrafamilial Phenotypic Variability in Individuals with Collagen-Related Osteogenesis Imperfecta
Clinical and translational science, Vol.13(5), pp.960-971
2020
PMCID: PMC7485955
PMID: 32166892
Abstract
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 alpha 1 and alpha 2 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.
Details
- Title
- Inter- and Intrafamilial Phenotypic Variability in Individuals with Collagen-Related Osteogenesis Imperfecta
- Authors/Creators
- Lidiia Zhytnik - University of TartuKatre Maasalu - Tartu University HospitalTiia Reimand - University of TartuBinh Ho Duy - Hue UniversitySulev Koks - Perron Institute for Neurological and Translational ScienceAare Martson - University of Tartu
- Publication Details
- Clinical and translational science, Vol.13(5), pp.960-971
- Publisher
- Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
- Number of pages
- 12
- Grant note
- IUT20-46 / Estonian Ministry of Education and Research; Ministry of Education and Research, Estonia Estonian Ministry of Education and Research; Ministry of Education and Research, Estonia 668989 / H2020 ERA-chair grant
- Identifiers
- 991005634027007891
- Copyright
- © 2020 The Authors.
- Murdoch Affiliation
- Personalised Medicine Centre
- Language
- English
- Resource Type
- Journal article
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