In: Respiratory Research, 12 (2011), Nr. 99. pp. 1-10. ISSN 1465-993X
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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.
Document type: | Article |
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Journal or Publication Title: | Respiratory Research |
Volume: | 12 |
Number: | 99 |
Publisher: | BioMed Central |
Place of Publication: | London |
Date Deposited: | 25 May 2016 12:21 |
Date: | 2011 |
ISSN: | 1465-993X |
Page Range: | pp. 1-10 |
Faculties / Institutes: | Medizinische Fakultät Heidelberg > Medizinische Universitäts-Klinik und Poliklinik Medizinische Fakultät Heidelberg > Institut für Humangenetik Medizinische Fakultät Heidelberg > Thoraxklinik Heidelberg gGmbH |
DDC-classification: | 610 Medical sciences Medicine |