Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2mutations
10
pages
English
Documents
2011
Obtenez un accès à la bibliothèque pour le consulter en ligne En savoir plus
Découvre YouScribe et accède à tout notre catalogue !
Découvre YouScribe et accède à tout notre catalogue !
10
pages
English
Documents
2011
Obtenez un accès à la bibliothèque pour le consulter en ligne En savoir plus
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.
Voir
Pfarret al.Respiratory Research2011,12:99 http://respiratoryresearch.com/content/12/1/99
R E S E A R C HOpen Access Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2mutations 1,2†2†2†2 1 Nicole Pfarr, Justyna SzamalekHoegel, Christine Fischer, Katrin Hinderhofer , Christian Nagel , 1 34 33 3 Nicola Ehlken , Henning Tiede , Horst Olschewski , Frank Reichenberger , Ardeschir HA Ghofrani , Werner Seeger 1* and Ekkehard Grünig
Abstract Background:Mutations in thebone morphogenetic protein receptor 2(BMPR2) gene can lead to idiopathic pulmonary arterial hypertension (IPAH). This study prospectively screened forBMPR2mutations in a large cohort of PAHpatients and compared clinical features betweenBMPR2mutation carriers and noncarriers. 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 noncarriers ofBMPR2mutations. In noncarriers with familial aggregation of PAH further genes/gene regions as theBMPR2promoter region, theACVRL1,Endoglin, andSMAD8genes 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 theBMPR2gene have been identified. TwelveBMPR2mutations and 3 unclassified sequence variants have not yet been described before. Mutation carriers were significantly younger at diagnosis than noncarriers (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 newBMPR2mutations, 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 forBMPR2mutations may be clinically useful.
Introduction Pulmonary arterial hypertension (PAH) is a rare vascular disorder characterised by increased pulmonary vascular resistance and right heart failure. PAH can be idiopathic (IPAH), heritable (HPAH) or associated with other con ditions (APAH) as connective tissue diseases, congenital heart diseases, portal hypertension, drug or toxin expo sure [1,2]. Heterozygous germline mutations in thebone morphogenetic protein type 2 receptor(BMPR2) have
* Correspondence: ekkehard.gruenig@thoraxklinikheidelberg.de †Contributed equally 1 Centre for Pulmonary Hypertension Thoraxclinic, University of Heidelberg, Heidelberg, Germany Full list of author information is available at the end of the article
been identified as a gene underlying HPAH in approxi mately 10 to 40% of patients with apparently sporadic disease [1,36] and in 58% to 74% of patients with famil ial PAH [1,4,6,7]. In total 298 different mutations in BMPR2have been identified so far in independent patients including those with a known PAH family his tory, sporadic disease and PAH associated with other diseases [1]. In a few PAH patients mutations in other genes participating in the BMPR2 signalling pathway have been identified, asActivin A receptor type IIlike 1 (ACVRL1, also calledALK1) [8],Endoglin[9], and SMAD8[10]. Nevertheless, there is still a small
© 2011 Pfarr et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
