Abstract
Pulmonary arterial hypertension (PAH) is a rare disease, which can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, termed bone morphogenetic protein receptor 2 (BMPR2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and health care professionals, are increasingly faced with a range of questions regarding the need for, approaches to and the benefits and risks, of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives, through the process of genetic counselling, and describe the presently known disease causal genes, to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH, include identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of Interest: Christina A. Eichstaedt reports lecture fees from MSD, outside the submitted work; and has patent “Gene panel specific for pulmonary hypertension and its uses” European Patent ID: EP3507380 issued.
Conflict of Interest: Catharina Belge reports consulting fees, participation on advisory board and lecture honoraria from Janssen, MSD/Bayer; travel support from MSD/Bayer; outside the submitted work.
Conflict of Interest: Wendy K. Chung reports scientific advisory board participation with Regeneron Genetics Center; outside the submitted work.
Conflict of Interest: Ekkehard Grünig reports grants from Actelion, Bayer, GSK, United Therapeutics, Novartis, Bellerophon, OMT, Pfizer, REATA; lecture fees and consultancy fees from Actelion, Bayer/MSD, GSK; travel support from Janssen; advisory board participation with MSD, Ferrer; outside the submitted work; and has patent “Gene panel specific for pulmonary hypertension and its uses” European Patent ID: EP3507380 issued. Ekkehard Grünig has also served in leadership roles for ADue and pH e.V., outside the submitted work.
Conflict of Interest: David Montani reports grants from Acceleron, Janssen, Merck; consulting fees from Acceleron; lecture honoraria from Bayer, Janssen, Merck; outside the submitted work.
Conflict of Interest: Richard C. Trembath reports lecture fees from Clinical Cases; outside the submitted work.
Conflict of Interest: Nicholas W. Morrell reports employment and stock/stock options from Centessa Pharmaceuticals.
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- Received July 22, 2022.
- Accepted October 7, 2022.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
