Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Pulmonary Arterial Hypertension (PAH) [I27.0]

OMIM numbers: 178600, 600799 (BMPR2)

Dipl.-Biol. Christine Schack, Dipl.-Biol. Christina Sofeso

Scientific Background

Pulmonary arterial hypertension (PAH) is a rare chronic and progressive vascular lung disease. PAH may occur sporadically without known cause (idiopathic pulmonary arterial hypertension, IPAH) or be familial (hereditary pulmonary arterial hypertension, HPAH). Furthermore, PAH may occur in association with other diseases (APAH) including connective tissue disease, portal hypertension or infection with HIV; it may also be induced by certain medication. PAH is characterized by a mean pulmonary arterial pressure (PAP) of ≥ 25mmHg at rest (assessed by right heart catheterization) and by increased pulmonary vascular resistance (PVR). The typical changes in the pulmonary vessels cause an increase in vasoconstriction and therefore right heart strain, which may lead to right ventricular failure.

Hereditary pulmonary arterial hypertension (HPAH) is an autosomal dominant disease with reduced penetrance. Heterozygous mutations (point mutations as well as larger deletions/duplications) in the BMPR2 gene (bone morphogenetic protein receptor type 2) have so far been identified in over 70% of cases where PAH occurs in a familial context (HPAH) and in 10-40% of IPAH patients with neither a family history of PAH nor an identified risk factor. Latter have most likely de novo mutations or are hereditary cases of which the familial background frequently remains undetected due to the low penetrance. Since PAH patients usually show non-specific signs and symptoms such as breathlessness, fatigue, exhaustion and exertional dyspnoea, 2-3 years may pass from the onset of the first signs and symptoms to the diagnosis of PAH. An early diagnosis is crucial for a successful therapy, since an early start of treatment has a significant impact on prognosis and quality of life. Moleculargenetic diagnostic procedures can complement the standard diagnostic procedures.