eprintid: 20742 rev_number: 13 eprint_status: archive userid: 1589 dir: disk0/00/02/07/42 datestamp: 2016-05-25 12:21:45 lastmod: 2024-04-15 03:17:38 status_changed: 2016-05-25 12:21:45 type: article metadata_visibility: show creators_name: Pfarr, Nicole creators_name: Szamalek-Hoegel, Justyna creators_name: Fischer, Christine creators_name: Hinderhofer, Katrin creators_name: Nagel, Christian creators_name: Ehlken, Nicola creators_name: Tiede, Henning creators_name: Olschewski, Horst creators_name: Reichenberger, Frank creators_name: Ghofrani, Ardeschir HA creators_name: Seeger, Werner creators_name: Grünig, Ekkehard title: Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations subjects: ddc-610 divisions: i-910100 divisions: i-911500 divisions: i-950900 abstract: Background: Mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene can lead to idiopathic pulmonary arterial hypertension (IPAH). This study prospectively screened for BMPR2 mutations in a large cohort of PAH-patients and compared clinical features between BMPR2 mutation carriers and non-carriers. Methods: 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 BMPR2 mutations. In non-carriers with familial aggregation of PAH further genes/gene regions as the BMPR2 promoter region, the ACVRL1, Endoglin, and SMAD8 genes have been analysed. Results: 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 BMPR2 gene have been identified. Twelve BMPR2 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. Conclusion: This study identified in a large prospectively assessed cohort of PAH- patients new BMPR2 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 BMPR2 mutations may be clinically useful. date: 2011 publisher: BioMed Central id_scheme: DOI ppn_swb: 1656792575 own_urn: urn:nbn:de:bsz:16-heidok-207420 language: eng bibsort: PFARRNICOLHEMODYNAMI2011 full_text_status: public publication: Respiratory Research volume: 12 number: 99 place_of_pub: London pagerange: 1-10 issn: 1465-993X citation: Pfarr, Nicole ; Szamalek-Hoegel, Justyna ; Fischer, Christine ; Hinderhofer, Katrin ; Nagel, Christian ; Ehlken, Nicola ; Tiede, Henning ; Olschewski, Horst ; Reichenberger, Frank ; Ghofrani, Ardeschir HA ; Seeger, Werner ; Grünig, Ekkehard (2011) Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations. Respiratory Research, 12 (99). pp. 1-10. ISSN 1465-993X document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/20742/1/12931_2011_Article_1129.pdf