In the present study we developed a new specific gene panel for pulmonary arterial hypertension (PAH) including major disease genes and further candidates. We assessed 37 patients with invasively confirmed PAH and five relatives of affected patients for genetic testing. A new PAH-specific gene panel was designed using next generation sequencing (NGS) including 12 known disease genes and 17 further candidates. Any potential pathogenic variants were reassessed by Sanger sequencing. Twenty-two of the 37 patients (59%) had a mutation in BMPR2, ALK1, ENG or EIF2AK4 genes identified by panel and Sanger sequencing. In addition, 12 unclassified variants were identified in seven genes (known and candidate genes). A sensitivity of 100% was met after quality parameters were adjusted. Specificity increased to 100% when Sanger technique was added as a routine validation. The new PAH-specific gene panel developed in the present study allowed for the first time the assessment of all known PAH genes and further candidates at once and markedly reduced overall sequencing time and costs. Sensitivity and specificity reached 100% when Sanger sequencing was additionally applied. Thus, this technique will potentially change the routine diagnostic genetic testing in PAH patients.
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The effect on lung function and respiratory symptoms of reducing of consumption of conventional cigarettes by switching to electronic cigarettes is investigated by the Cibella et al. in their Clinical Science research article on pages 1929-1937 (volume 130, issue 21).
Research Article|
October 11 2016
Identification of genetic defects in pulmonary arterial hypertension by a new gene panel diagnostic tool
Jie Song;
Jie Song
1
*Centre for Pulmonary Hypertension at Thoraxclinic, University Hospital Heidelberg, Röntgenstraße 1, 69126 Heidelberg, Germany
†Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
‡Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany
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Christina A. Eichstaedt;
Christina A. Eichstaedt
1
*Centre for Pulmonary Hypertension at Thoraxclinic, University Hospital Heidelberg, Röntgenstraße 1, 69126 Heidelberg, Germany
†Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
‡Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany
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Rebecca Rodríguez Viales;
Rebecca Rodríguez Viales
§Research Unit for Genome Biology, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany
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Nicola Benjamin;
Nicola Benjamin
*Centre for Pulmonary Hypertension at Thoraxclinic, University Hospital Heidelberg, Röntgenstraße 1, 69126 Heidelberg, Germany
‡Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany
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Satenik Harutyunova;
Satenik Harutyunova
*Centre for Pulmonary Hypertension at Thoraxclinic, University Hospital Heidelberg, Röntgenstraße 1, 69126 Heidelberg, Germany
‡Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany
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Christine Fischer;
Christine Fischer
†Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
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Ekkehard Grünig;
Ekkehard Grünig
*Centre for Pulmonary Hypertension at Thoraxclinic, University Hospital Heidelberg, Röntgenstraße 1, 69126 Heidelberg, Germany
‡Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany
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Katrin Hinderhofer
†Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
Correspondence: Katrin Hinderhofer (email [email protected])
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Publisher: Portland Press Ltd
Received:
July 12 2016
Revision Received:
September 02 2016
Accepted:
September 09 2016
Accepted Manuscript online:
September 09 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (22): 2043–2052.
Article history
Received:
July 12 2016
Revision Received:
September 02 2016
Accepted:
September 09 2016
Accepted Manuscript online:
September 09 2016
Citation
Jie Song, Christina A. Eichstaedt, Rebecca Rodríguez Viales, Nicola Benjamin, Satenik Harutyunova, Christine Fischer, Ekkehard Grünig, Katrin Hinderhofer; Identification of genetic defects in pulmonary arterial hypertension by a new gene panel diagnostic tool. Clin Sci (Lond) 1 November 2016; 130 (22): 2043–2052. doi: https://doi.org/10.1042/CS20160531
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