Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations

• Verfasst von: Pfarr, Nicole [VerfasserIn]
• Verfasst von: Szamalek-Hoegel, Justyna [VerfasserIn]
• Verfasst von: Fischer, Christine [VerfasserIn]
• Verfasst von: Hinderhofer, Katrin [VerfasserIn]
• Verfasst von: Nagel, Christian [VerfasserIn]
• Verfasst von: Benjamin, Nicola [VerfasserIn]
• Verfasst von: Tiede, Henning [VerfasserIn]
• Verfasst von: Olschewski, Horst [VerfasserIn]
• Verfasst von: Reichenberger, Frank [VerfasserIn]
• Verfasst von: Ghofrani, Ardeschir H. A. [VerfasserIn]
• Verfasst von: Seeger, Werner [VerfasserIn]
• Verfasst von: Grünig, Ekkehard [VerfasserIn]
• Titel: Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations
• Verf.angabe: Nicole Pfarr, Justyna Szamalek-Hoegel, Christine Fischer, Katrin Hinderhofer, Christian Nagel, Nicola Ehlken, Henning Tiede, Horst Olschewski, Frank Reichenberger, Ardeschir H. A. Ghofrani, Werner Seeger and Ekkehard Grünig
• E-Jahr: 2011
• Jahr: 29 July 2011
• Umfang: 10 S.
• Fussnoten: Gesehen am 08.12.2022
• Titel Quelle: Enthalten in: Respiratory research
• Ort Quelle: London : BioMed Central, 2001
• Jahr Quelle: 2011
• Band/Heft Quelle: 12(2011), 1, Artikel-ID 99, Seite 1-10
• ISSN Quelle: 1465-993X
• DOI: doi:10.1186/1465-9921-12-99
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adolescent
• Sach-SW: Adult
• Sach-SW: Age of Onset
• Sach-SW: Aged
• Sach-SW: Bone Morphogenetic Protein Receptors, Type II
• Sach-SW: Cardiac Catheterization
• Sach-SW: Case-Control Studies
• Sach-SW: DNA Mutational Analysis
• Sach-SW: Familial Primary Pulmonary Hypertension
• Sach-SW: Female
• Sach-SW: Gene Frequency
• Sach-SW: Genetic Predisposition to Disease
• Sach-SW: Genetic Testing
• Sach-SW: Germany
• Sach-SW: Hemodynamics
• Sach-SW: Heredity
• Sach-SW: Humans
• Sach-SW: Hypertension, Pulmonary
• Sach-SW: Male
• Sach-SW: Middle Aged
• Sach-SW: Mutation
• Sach-SW: Pedigree
• Sach-SW: Phenotype
• Sach-SW: Prospective Studies
• Sach-SW: Severity of Illness Index
• Sach-SW: Young Adult
• K10plus-PPN: 1826625852

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.