Genetic Predisposition to High-Altitude Pulmonary Edema
Christina A Eichstaedt1,2,3, Heimo Mairbäurl3,4, Jie Song1,2,5
1Center for Pulmonary Hypertension, Thoraxclinic at the University Hospital Heidelberg, Heidelberg, Germany.
High Altitude Medicine & Biology
|January 25, 2020
Summary
Genetic analysis revealed a likely pathogenic mutation in the JAK2 gene in a family with high-altitude pulmonary edema (HAPE). This finding suggests a genetic predisposition to HAPE and pulmonary arterial hypertension (PAH) in some individuals.
Area of Science:
- Genetics
- Physiology
- Altitude Medicine
Background:
- Exaggerated pulmonary arterial hypertension (PAH) is a key characteristic of high-altitude pulmonary edema (HAPE).
- Understanding the genetic factors contributing to HAPE susceptibility is crucial for prevention and treatment.
Purpose of the Study:
- To investigate the genetic predisposition to HAPE by examining PAH candidate genes.
- To analyze a HAPE-susceptible (HAPE-S) family and unrelated HAPE-S mountaineers for genetic variants.
Main Methods:
- Clinical and genetic assessment of eight family members and 64 mountaineers.
- Next-generation sequencing using a PAH-specific gene panel (42 genes).
Main Results:
- A likely pathogenic missense mutation (c.1198T>G p.Cys400Gly) in the Janus Kinase 2 (JAK2) gene was identified in two family members with a history of re-entry HAPE.
- One family member with the JAK2 mutation developed mild PAH.
- Likely pathogenic variants were detected in 3.1% of HAPE-S mountaineers (Cytochrome P1B1 and HRG genes).
Conclusions:
- This study is the first to identify an inherited missense mutation in a PAH-related gene in a HAPE family with progression to borderline PAH.
- The presence of likely pathogenic variants in HAPE-S mountaineers suggests a genetic predisposition linked to PAH signaling pathways.
Keywords:
genetic factorshigh-altitude pulmonary edemahypoxic pulmonary vasoconstrictionpredispositionpulmonary hypertensionMore Related Videos
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