Christina A. Eichstaedt, Heimo Mairbäurl, Jie Song, Nicola Benjamin, Christine Fischer, Christoph Dehnert, Kai Schommer, Marc M. Berger, Peter Bärtsch, Ekkehard Grünig, Katrin Hinderhofer
University Hospital Heidelberg and Heidelberg University. Second Xiangya Hospital and Central South University. Medbase Checkup Center. University Hospital Salzburg and Paracelsus Medical University.
Germany, China, Switzerland and Austria
High Altitude Medicine and Biology
High Alt Med Biol 2020; 21: 28-36
DOI: 10.1089/ham.2019.0083
Abstract
Background: Exaggerated pulmonary arterial hypertension (PAH) is a hallmark of high-altitude pulmonary edema (HAPE). The objective of this study was therefore to investigate genetic predisposition to HAPE by analyzing PAH candidate genes in a HAPE-susceptible (HAPE-S) family and in unrelated HAPE-S mountaineers.
Materials and Methods: Eight family members and 64 mountaineers were clinically and genetically assessed using a PAH-specific gene panel for 42 genes by next-generation sequencing.
Results: Two otherwise healthy family members, who developed re-entry HAPE at 3640 m during childhood, carried a likely pathogenic missense mutation (c.1198T>G p.Cys400Gly) in the Janus Kinase 2 (JAK2) gene. One of them progressed to a mild form of PAH at the age of 23 years. In two of the 64 HAPE-S mountaineers likely pathogenic variants have been detected, one missense mutation in the Cytochrome P1B1 gene, and a deletion in the Histidine-Rich Glycoprotein (HRG) gene.
Conclusions: This is the first study identifying an inherited missense mutation of a gene related to PAH in a family with re-entry HAPE showing a progression to borderline PAH in the index patient. Likely pathogenic variants in 3.1% of HAPE-S mountaineers suggest a genetic predisposition in some individuals that might be linked to PAH signaling pathways.
Category
High Altitude Pulmonary Edema
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes