Genetic diagnostics in patients with chronic thromboembolic pulmonary hypertension

Le résumé fourni par la source

While 85% of heritable pulmonary arterial hypertension patients carry mutations within the bone morphogenetic protein receptor 2 (BMPR2) gene or associated pathway genes, possible underlying genetic predisposition to chronic thromboembolic pulmonary hypertension (CTEPH) is largely unexplored. Only few case reports of CTEPH patients with mutations exist. Hence, genetic diagnostics is not recommended by current guidelines for this patient population. The objective of this study was to analyse whether PAH gene mutations are more common in CTEPH patients than previously thought. A systematic screening was conducted for mutations in 13 PAH and 30 additional candidate genes using a PAH specific gene panel based on next generation sequencing. CTEPH was diagnosed according to current guidelines. Out of 33 CTEPH patients 3 (9.1%) carried pathogenic variants, 8 further patients (24.2%) carried variants of unknown significance in 2 PAH and 6 further candidate genes. One patient had a nonsense mutation (c.2071A>T/p.(Lys691*) within the BMPR2 gene and two further patients carried a missense mutation (c.1849G>T/p.Val617Phe) in the Janus Kinase 2 (JAK2) gene, which is well known from polycythemia vera. Both CTEPH patients with the JAK2 mutation suffered also from a myeloproliferative disease. This study could identify mutations in about 10% of the CTEPH patients. Hence, CTEPH patients may have a genetic predisposition more often than previously thought. The predisposition for polycythemia vera could be an additional risk factor for CTEPH development. Thus, genetic diagnostics may be considered also for CTEPH patients to investigate an hereditary component.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.