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From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classifica...

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Autores principales: Storoni, Silvia, Verdonk, Sara J. E., Zhytnik, Lidiia, Pals, Gerard, Treurniet, Sanne, Elting, Mariet W., Sakkers, Ralph J. B., van den Aardweg, Joost G., Eekhoff, Elisabeth M. W., Micha, Dimitra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953243/
https://www.ncbi.nlm.nih.gov/pubmed/36830650
http://dx.doi.org/10.3390/biom13020281
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author Storoni, Silvia
Verdonk, Sara J. E.
Zhytnik, Lidiia
Pals, Gerard
Treurniet, Sanne
Elting, Mariet W.
Sakkers, Ralph J. B.
van den Aardweg, Joost G.
Eekhoff, Elisabeth M. W.
Micha, Dimitra
author_facet Storoni, Silvia
Verdonk, Sara J. E.
Zhytnik, Lidiia
Pals, Gerard
Treurniet, Sanne
Elting, Mariet W.
Sakkers, Ralph J. B.
van den Aardweg, Joost G.
Eekhoff, Elisabeth M. W.
Micha, Dimitra
author_sort Storoni, Silvia
collection PubMed
description Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classification only partially takes into account extraskeletal manifestations and the high genetic variability. Little is known about the relation between genetic variants and phenotype as of yet. The aim of the study was to create a clinically relevant genetic stratification of a cohort of 675 Dutch OI patients based on their pathogenic variant types and to provide an overview of their respective medical care demands. The clinical records of 675 OI patients were extracted from the Amsterdam UMC Genome Database and matched with the records from Statistics Netherlands (CBS). The patients were categorized based on their harbored pathogenic variant. The information on hospital admissions, outpatient clinic visits, medication, and diagnosis-treatment combinations (DTCs) was compared between the variant groups. OI patients in the Netherlands appear to have a higher number of DTCs, outpatient clinic visits, and hospital admissions when compared to the general Dutch population. Furthermore, medication usage seems higher in the OI cohort in comparison to the general population. The patients with a COL1A1 or COL1A2 dominant negative missense non-glycine substitution appear to have a lower health care need compared to the other groups, and even lower than patients with COL1A1 or COL1A2 haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient’s phenotype.
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spelling pubmed-99532432023-02-25 From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients Storoni, Silvia Verdonk, Sara J. E. Zhytnik, Lidiia Pals, Gerard Treurniet, Sanne Elting, Mariet W. Sakkers, Ralph J. B. van den Aardweg, Joost G. Eekhoff, Elisabeth M. W. Micha, Dimitra Biomolecules Article Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classification only partially takes into account extraskeletal manifestations and the high genetic variability. Little is known about the relation between genetic variants and phenotype as of yet. The aim of the study was to create a clinically relevant genetic stratification of a cohort of 675 Dutch OI patients based on their pathogenic variant types and to provide an overview of their respective medical care demands. The clinical records of 675 OI patients were extracted from the Amsterdam UMC Genome Database and matched with the records from Statistics Netherlands (CBS). The patients were categorized based on their harbored pathogenic variant. The information on hospital admissions, outpatient clinic visits, medication, and diagnosis-treatment combinations (DTCs) was compared between the variant groups. OI patients in the Netherlands appear to have a higher number of DTCs, outpatient clinic visits, and hospital admissions when compared to the general Dutch population. Furthermore, medication usage seems higher in the OI cohort in comparison to the general population. The patients with a COL1A1 or COL1A2 dominant negative missense non-glycine substitution appear to have a lower health care need compared to the other groups, and even lower than patients with COL1A1 or COL1A2 haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient’s phenotype. MDPI 2023-02-02 /pmc/articles/PMC9953243/ /pubmed/36830650 http://dx.doi.org/10.3390/biom13020281 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Storoni, Silvia
Verdonk, Sara J. E.
Zhytnik, Lidiia
Pals, Gerard
Treurniet, Sanne
Elting, Mariet W.
Sakkers, Ralph J. B.
van den Aardweg, Joost G.
Eekhoff, Elisabeth M. W.
Micha, Dimitra
From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients
title From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients
title_full From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients
title_fullStr From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients
title_full_unstemmed From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients
title_short From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients
title_sort from genetics to clinical implications: a study of 675 dutch osteogenesis imperfecta patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953243/
https://www.ncbi.nlm.nih.gov/pubmed/36830650
http://dx.doi.org/10.3390/biom13020281
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