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Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease which is often caused by recurrent emboli. These are also frequently found in patients with myeloproliferative diseases. While myeloproliferative diseases can be caused by gene defects, the genetic predisposition to CTEPH is lar...

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Autores principales: Eichstaedt, Christina A., Verweyen, Jeremias, Halank, Michael, Benjamin, Nicola, Fischer, Christine, Mayer, Eckhard, Guth, Stefan, Wiedenroth, Christoph B., Egenlauf, Benjamin, Harutyunova, Satenik, Xanthouli, Panagiota, Marra, Alberto M., Wilkens, Heinrike, Ewert, Ralf, Hinderhofer, Katrin, Grünig, Ekkehard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246715/
https://www.ncbi.nlm.nih.gov/pubmed/32397294
http://dx.doi.org/10.3390/ijms21093339
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author Eichstaedt, Christina A.
Verweyen, Jeremias
Halank, Michael
Benjamin, Nicola
Fischer, Christine
Mayer, Eckhard
Guth, Stefan
Wiedenroth, Christoph B.
Egenlauf, Benjamin
Harutyunova, Satenik
Xanthouli, Panagiota
Marra, Alberto M.
Wilkens, Heinrike
Ewert, Ralf
Hinderhofer, Katrin
Grünig, Ekkehard
author_facet Eichstaedt, Christina A.
Verweyen, Jeremias
Halank, Michael
Benjamin, Nicola
Fischer, Christine
Mayer, Eckhard
Guth, Stefan
Wiedenroth, Christoph B.
Egenlauf, Benjamin
Harutyunova, Satenik
Xanthouli, Panagiota
Marra, Alberto M.
Wilkens, Heinrike
Ewert, Ralf
Hinderhofer, Katrin
Grünig, Ekkehard
author_sort Eichstaedt, Christina A.
collection PubMed
description Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease which is often caused by recurrent emboli. These are also frequently found in patients with myeloproliferative diseases. While myeloproliferative diseases can be caused by gene defects, the genetic predisposition to CTEPH is largely unexplored. Therefore, the objective of this study was to analyse these genes and further genes involved in pulmonary hypertension in CTEPH patients. A systematic screening was conducted for pathogenic variants using a gene panel based on next generation sequencing. CTEPH was diagnosed according to current guidelines. In this study, out of 40 CTEPH patients 4 (10%) carried pathogenic variants. One patient had a nonsense variant (c.2071A>T p.Lys691*) in the BMPR2 gene and three further patients carried the same pathogenic variant (missense variant, c.1849G>T p.Val617Phe) in the Janus kinase 2 (JAK2) gene. The latter led to a myeloproliferative disease in each patient. The prevalence of this JAK2 variant was significantly higher than expected (p < 0.0001). CTEPH patients may have a genetic predisposition more often than previously thought. The predisposition for myeloproliferative diseases could be an additional risk factor for CTEPH development. Thus, clinical screening for myeloproliferative diseases and genetic testing may be considered also for CTEPH patients.
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spelling pubmed-72467152020-06-10 Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study Eichstaedt, Christina A. Verweyen, Jeremias Halank, Michael Benjamin, Nicola Fischer, Christine Mayer, Eckhard Guth, Stefan Wiedenroth, Christoph B. Egenlauf, Benjamin Harutyunova, Satenik Xanthouli, Panagiota Marra, Alberto M. Wilkens, Heinrike Ewert, Ralf Hinderhofer, Katrin Grünig, Ekkehard Int J Mol Sci Article Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease which is often caused by recurrent emboli. These are also frequently found in patients with myeloproliferative diseases. While myeloproliferative diseases can be caused by gene defects, the genetic predisposition to CTEPH is largely unexplored. Therefore, the objective of this study was to analyse these genes and further genes involved in pulmonary hypertension in CTEPH patients. A systematic screening was conducted for pathogenic variants using a gene panel based on next generation sequencing. CTEPH was diagnosed according to current guidelines. In this study, out of 40 CTEPH patients 4 (10%) carried pathogenic variants. One patient had a nonsense variant (c.2071A>T p.Lys691*) in the BMPR2 gene and three further patients carried the same pathogenic variant (missense variant, c.1849G>T p.Val617Phe) in the Janus kinase 2 (JAK2) gene. The latter led to a myeloproliferative disease in each patient. The prevalence of this JAK2 variant was significantly higher than expected (p < 0.0001). CTEPH patients may have a genetic predisposition more often than previously thought. The predisposition for myeloproliferative diseases could be an additional risk factor for CTEPH development. Thus, clinical screening for myeloproliferative diseases and genetic testing may be considered also for CTEPH patients. MDPI 2020-05-08 /pmc/articles/PMC7246715/ /pubmed/32397294 http://dx.doi.org/10.3390/ijms21093339 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Eichstaedt, Christina A.
Verweyen, Jeremias
Halank, Michael
Benjamin, Nicola
Fischer, Christine
Mayer, Eckhard
Guth, Stefan
Wiedenroth, Christoph B.
Egenlauf, Benjamin
Harutyunova, Satenik
Xanthouli, Panagiota
Marra, Alberto M.
Wilkens, Heinrike
Ewert, Ralf
Hinderhofer, Katrin
Grünig, Ekkehard
Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study
title Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study
title_full Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study
title_fullStr Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study
title_full_unstemmed Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study
title_short Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension—A Genetic Study
title_sort myeloproliferative diseases as possible risk factor for development of chronic thromboembolic pulmonary hypertension—a genetic study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246715/
https://www.ncbi.nlm.nih.gov/pubmed/32397294
http://dx.doi.org/10.3390/ijms21093339
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