Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and <it>BMPR2 </it>mutations

• Main Authors: Tiede Henning, Ehlken Nicola, Nagel Christian, Hinderhofer Katrin, Fischer Christine, Szamalek-Hoegel Justyna, Pfarr Nicole, Olschewski Horst, Reichenberger Frank, Ghofrani Ardeschir HA, Seeger Werner, Grünig Ekkehard
• Format: Article
• Language: English
• Published: BMC 2011-07-01
• Series: Respiratory Research
• Online Access: http://respiratory-research.com/content/12/1/99

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>bone morphogenetic protein receptor 2 </it>(<it>BMPR2</it>) gene can lead to idiopathic pulmonary arterial hypertension (IPAH). This study prospectively screened for <it>BMPR2 </it>mutations in a large cohort of PAH-patients and compared clinical features between <it>BMPR2 </it>mutation carriers and non-carriers.</p> <p>Methods</p> <p>Patients have been assessed by right heart catheterization and genetic testing. In all patients a detailed family history and pedigree analysis have been obtained. We compared age at diagnosis and hemodynamic parameters between carriers and non-carriers of <it>BMPR2 </it>mutations. In non-carriers with familial aggregation of PAH further genes/gene regions as the <it>BMPR2 </it>promoter region, the <it>ACVRL1</it>, <it>Endoglin</it>, and <it>SMAD8 </it>genes have been analysed.</p> <p>Results</p> <p>Of the 231 index patients 22 revealed a confirmed familial aggregation of the disease (HPAH), 209 patients had sporadic IPAH. In 49 patients (86.3% of patients with familial aggregation and 14.3% of sporadic IPAH) mutations of the <it>BMPR2 </it>gene have been identified. Twelve <it>BMPR2 </it>mutations and 3 unclassified sequence variants have not yet been described before. Mutation carriers were significantly younger at diagnosis than non-carriers (38.53 ± 12.38 vs. 45.78 ± 11.32 years, p < 0.001) and had a more severe hemodynamic compromise. No gene defects have been detected in 3 patients with HPAH.</p> <p>Conclusion</p> <p>This study identified in a large prospectively assessed cohort of PAH- patients new <it>BMPR2 </it>mutations, which have not been described before and confirmed previous findings that mutation carriers are younger at diagnosis with a more severe hemodynamic compromise. Thus, screening for <it>BMPR2 </it>mutations may be clinically useful.</p>