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Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension
BACKGROUND: A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in othe...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962083/ https://www.ncbi.nlm.nih.gov/pubmed/35346192 http://dx.doi.org/10.1186/s12931-022-01987-x |
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author | Eichstaedt, Christina A. Saßmannshausen, Zoe Shaukat, Memoona Cao, Ding Xanthouli, Panagiota Gall, Henning Sommer, Natascha Ghofrani, Hossein-Ardeschir Seyfarth, Hans-Jürgen Lerche, Marianne Halank, Michael Kleymann, Janina Benjamin, Nicola Harutyunova, Satenik Egenlauf, Benjamin Milger, Katrin Rosenkranz, Stephan Ewert, Ralf Klose, Hans Hoeper, Marius M. Olsson, Karen M. Lankeit, Mareike Lange, Tobias J. Hinderhofer, Katrin Grünig, Ekkehard |
author_facet | Eichstaedt, Christina A. Saßmannshausen, Zoe Shaukat, Memoona Cao, Ding Xanthouli, Panagiota Gall, Henning Sommer, Natascha Ghofrani, Hossein-Ardeschir Seyfarth, Hans-Jürgen Lerche, Marianne Halank, Michael Kleymann, Janina Benjamin, Nicola Harutyunova, Satenik Egenlauf, Benjamin Milger, Katrin Rosenkranz, Stephan Ewert, Ralf Klose, Hans Hoeper, Marius M. Olsson, Karen M. Lankeit, Mareike Lange, Tobias J. Hinderhofer, Katrin Grünig, Ekkehard |
author_sort | Eichstaedt, Christina A. |
collection | PubMed |
description | BACKGROUND: A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in other PAH forms remains uncertain. We present the distribution of mutations across PAH genes identified at the largest German referral centre for genetic diagnostics in PAH over a course of > 3 years. METHODS: Our PAH-specific gene diagnostics panel was used to sequence 325 consecutive PAH patients from March 2017 to October 2020. For the first year the panel contained thirteen PAH genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4. These were extended by the three genes ATP13A3, AQP1 and SOX17 from March 2018 onwards following the genes’ discovery. RESULTS: A total of 79 mutations were identified in 74 patients (23%). Of the variants 51 (65%) were located in the gene BMPR2 while the other 28 variants were found in ten further PAH genes. We identified disease-causing variants in the genes AQP1, KCNK3 and SOX17 in families with at least two PAH patients. Mutations were not only detected in patients with heritable and idiopathic but also with associated PAH. CONCLUSIONS: Genetic defects were identified in 23% of the patients in a total of 11 PAH genes. This illustrates the benefit of the specific gene panel containing all known PAH genes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-01987-x. |
format | Online Article Text |
id | pubmed-8962083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89620832022-03-30 Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension Eichstaedt, Christina A. Saßmannshausen, Zoe Shaukat, Memoona Cao, Ding Xanthouli, Panagiota Gall, Henning Sommer, Natascha Ghofrani, Hossein-Ardeschir Seyfarth, Hans-Jürgen Lerche, Marianne Halank, Michael Kleymann, Janina Benjamin, Nicola Harutyunova, Satenik Egenlauf, Benjamin Milger, Katrin Rosenkranz, Stephan Ewert, Ralf Klose, Hans Hoeper, Marius M. Olsson, Karen M. Lankeit, Mareike Lange, Tobias J. Hinderhofer, Katrin Grünig, Ekkehard Respir Res Research BACKGROUND: A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in other PAH forms remains uncertain. We present the distribution of mutations across PAH genes identified at the largest German referral centre for genetic diagnostics in PAH over a course of > 3 years. METHODS: Our PAH-specific gene diagnostics panel was used to sequence 325 consecutive PAH patients from March 2017 to October 2020. For the first year the panel contained thirteen PAH genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4. These were extended by the three genes ATP13A3, AQP1 and SOX17 from March 2018 onwards following the genes’ discovery. RESULTS: A total of 79 mutations were identified in 74 patients (23%). Of the variants 51 (65%) were located in the gene BMPR2 while the other 28 variants were found in ten further PAH genes. We identified disease-causing variants in the genes AQP1, KCNK3 and SOX17 in families with at least two PAH patients. Mutations were not only detected in patients with heritable and idiopathic but also with associated PAH. CONCLUSIONS: Genetic defects were identified in 23% of the patients in a total of 11 PAH genes. This illustrates the benefit of the specific gene panel containing all known PAH genes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-01987-x. BioMed Central 2022-03-27 2022 /pmc/articles/PMC8962083/ /pubmed/35346192 http://dx.doi.org/10.1186/s12931-022-01987-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Eichstaedt, Christina A. Saßmannshausen, Zoe Shaukat, Memoona Cao, Ding Xanthouli, Panagiota Gall, Henning Sommer, Natascha Ghofrani, Hossein-Ardeschir Seyfarth, Hans-Jürgen Lerche, Marianne Halank, Michael Kleymann, Janina Benjamin, Nicola Harutyunova, Satenik Egenlauf, Benjamin Milger, Katrin Rosenkranz, Stephan Ewert, Ralf Klose, Hans Hoeper, Marius M. Olsson, Karen M. Lankeit, Mareike Lange, Tobias J. Hinderhofer, Katrin Grünig, Ekkehard Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension |
title | Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension |
title_full | Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension |
title_fullStr | Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension |
title_full_unstemmed | Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension |
title_short | Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension |
title_sort | gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962083/ https://www.ncbi.nlm.nih.gov/pubmed/35346192 http://dx.doi.org/10.1186/s12931-022-01987-x |
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