Pneumologie 2020; 74(S 01): 22
DOI: 10.1055/s-0039-3403109
Posterbegehung (PO02) – Sektion Zellbiologie
Neue Innovationen in der Zellbiologie
Georg Thieme Verlag KG Stuttgart · New York

Genetic findings in patients with different forms of pulmonary hypertension

C Eichstaedt
1   Zentrum für Pulmonale Hypertonie, Thoraxklinik am Universitätsklinikum Heidelberg; Translational Lung Research Centre Heidelberg (Tlrc), German Centre for Lung Research (Dzl); Institut für Humangenetik, Universität Heidelberg
,
Z Saßmannshausen
2   Laboratory for Molecular Diagnostics, Institute of Human Genetics, Heidelberg University
,
H Gall
3   Medizinische Klink II, Abteilung Pneumologie, Ukgm, Standort Gießen
,
HJ Seyfarth
4   Medizinische Klinik 1, Pneumologie, Universitätsklinikum Leipzig
,
M Lerche
5   Abteilung für Pneumologie, Universitätsklinikum Leipzig
,
M Halank
6   Medizinische Klinik und Poliklinik I, Univsitätsklinikum Dresden; Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
,
P Xanthouli
7   Centre for Pulmonary Hypertension at Thoraxklinik at University Hospital; Translational Lung Research Centre Heidelberg (Tlrc), German Centre for Lung Research (Dzl)
,
S Harutyunova
7   Centre for Pulmonary Hypertension at Thoraxklinik at University Hospital; Translational Lung Research Centre Heidelberg (Tlrc), German Centre for Lung Research (Dzl)
,
B Egenlauf
7   Centre for Pulmonary Hypertension at Thoraxklinik at University Hospital; Translational Lung Research Centre Heidelberg (Tlrc), German Centre for Lung Research (Dzl)
,
K Milger
8   Medizinische Klinik V, Comprehensive Pneumology Center (Cpc-M), Mitglied des Dzl, Klinikum der Universität München; Department of Internal Medicine V, Ludwig-Maximilians-University of Munich, Munich, Germany; Comprehensive Pneumology Center (Cpc-M), Member of the German Center for Lung Research (Dzl), Munich, Germany
,
S Rosenkranz
9   Department of Cardiology, University of Cologne; Department III of Internal Medicine and Cologne Cardiovascular Research Center (Ccrc), Cologne University Heart Center, Cologne
,
R Ewert
10   Zentrum für Innere Medizin, Klinik für Innere B, Bereich Pneumologie, Universitätsmedizin Greifswald Körperschaft des Öffentlichen Rechts
,
M Lankeit
11   Medizinische Klinik mit Schwerpunkt Kardiologie, Campus Virchow Klinikum, Charité; Universitätsmedizin Berlin
,
TJ Lange
12   Innere Medizin II, Pneumologie, Uniklinik Regensburg
,
K Hinderhofer
13   Institut für Humangenetik, Universität Heidelberg; Laboratory for Molecular Diagnostics, Institute of Human Genetics, Heidelberg University
,
E Grünig
7   Centre for Pulmonary Hypertension at Thoraxklinik at University Hospital; Translational Lung Research Centre Heidelberg (Tlrc), German Centre for Lung Research (Dzl)
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Publikationsverlauf

Publikationsdatum:
28. Februar 2020 (online)

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Background: A genetic predisposition has been identified in different forms of pulmonary arterial hypertension (PAH). Most pathogenic variants have been identified in BMPR2 in hereditary PAH. However, many further PAH genes have been described.

Objective: The aim of this study was to screen for all known PAH genes in a large cohort of patients with PAH and other forms of PH who have been referred for genetic testing.

Methods: DNA from 244 patients was extracted and sequenced using a PAH specific gene diagnostics panel for the genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4. Of these, 180 samples were also sequenced for ATP13A3, AQP1 and SOX17.

Results: Of the 244 patients 48% were classified as IPAH, 17% as HPAH, 11% as congenital heart disease associated PAH, 6% as connective tissue disease associated PAH and 8% as pulmonary veno-occlusive disease (PVOD). Included were also patients with sarcoidosis associated PH (n = 7), patients with Osler-Weber-Rendu syndrome (HHT, n = 6), portal hypertension (n = 3), persistent PH of the newborn (n = 3) and drug induced PAH (n = 3). A total of 60 pathogenic variants were identified, of which 53% were located in the gene BMPR2 but the others were found in the genes EIF2AK4, SOX17, KCNK3, ACVRL1, ENG, TBX4, GDF2, AQP1, ATP13A3, KCNA5 and SMAD9. Most HPAH patients had pathogenic variants in BMPR2 but also in AQP1, EIF2AK4, KCNK3, SMAD9 and SOX17. Patients with PVOD and HHT showed pathogenic variants in EIF2AK4, ENG and ACVRL1. Two sarcoidosis associated PH patients carried pathogenic variants in the genes GDF2 and SOX17.

Conclusion: Pathogenic variants were located in BMPR2 and in further PAH genes. Genetic predisposition was not restricted to HPAH, IPAH and PVOD but could also be identified in PH with sarcoidosis and other forms of associated PAH. Thus, genetic diagnostics might be useful in a larger patient cohort than currently recommended in the guidelines.