Genetische Grundlagen, Beratung und Testung bei Patienten mit pulmonalarterieller Hypertonie

Zusammenfassung

Die pulmonalarterielle Hypertonie (PAH) ist eine seltene und schwere Erkrankung, die durch einen erhöhten pulmonalarteriellen Mitteldruck und einen erhöhten pulmonalvaskulären Widerstand charakterisiert ist. Sie hat in vielen Fällen eine genetische Ursache, so findet man bei 85% der hereditären und bei ca. 15% der idiopathischen Fälle pathogene Varianten in PAH-spezifischen Genen. Am häufigsten ist das Gen des Bone Morphogenetic Protein Receptor Type 2 (BMPR2) betroffen. Es wurden jedoch in den letzten Jahren 17 weitere Gene größtenteils aus dem Signalweg des BMPR2-Gens entdeckt, die bei der diagnostischen Abklärung mit untersucht werden sollten. Dieser Artikel beschäftigt sich mit den molekulargenetischen Grundlagen der Erkrankung, dem Stellenwert der genetischen Beratung und Testung in den neuen Leitlinien sowie mit den wichtigsten Genen und den Verfahren, mit welchen man diese auf pathogene Varianten untersuchen kann. Die genetische Untersuchung kann einen Beitrag zur korrekten Diagnosestellung und zur Prognoseverbesserung der Patienten leisten und sollte auch gesunden Familienmitgliedern angeboten werden.

Abstract

Pulmonary arterial hypertension (PAH) is a rare and progressive disease. It is characterized by increased pulmonary arterial pressure and resistance. Genetic causes can be identified in 85% of hereditary PAH and 15% of idiopathic PAH patients. The main gene remains the bone morphogenetic protein receptor type 2 (BMPR2). However, 17 other PAH genes mainly associated with the BMPR2 signalling pathway have been reported and warrant genetic testing. The new guidelines strengthen the value of genetic counselling and testing for PAH patients and healthy family members of patients with disease causing variants. In this article, we shed light on the genetic background of PAH, how genetic screening is performed and how it may help to decide upon a differential diagnosis. We also explain the procedure of genetic testing and how the results should be communicated to the patients within the legal frame work.

Schlüsselwörter

Bone Morphogenetic Protein Receptor Type 2 - Panel-Sequenzierung - Next-Generation-Sequencing - Gendiagnostikgesetz - pulmonalarterielle Hypertonie

Keywords

pulmonary arterial hypertension - panel sequencing - next-generation-sequencing - genetic diagnostics law - bone morphogenetic protein receptor 2 gene

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