Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension

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• 作者：Nicole Pfarr (1) (2)
  Christine Fischer (1)
  Nicola Ehlken (2)
  Tabea Becker-Grünig (2)
  Vanesa López-González (3)
  Matthias Gorenflo (4)
  Alfred Hager (5)
  Katrin Hinderhofer (1)
  Oliver Miera (6)
  Christian Nagel (2)
  Dietmar Schranz (7)
  Ekkehard Grünig (2)
  
• 关键词：Pulmonary hypertension ; Congenital heart disease ; Genetics ; Children ; Bone morphogenetic protein receptor 2
• 刊名：Respiratory Research
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：14
• 期：1
• 全文大小：272KB
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• 作者单位：Nicole Pfarr (1) (2)
  Christine Fischer (1)
  Nicola Ehlken (2)
  Tabea Becker-Grünig (2)
  Vanesa López-González (3)
  Matthias Gorenflo (4)
  Alfred Hager (5)
  Katrin Hinderhofer (1)
  Oliver Miera (6)
  Christian Nagel (2)
  Dietmar Schranz (7)
  Ekkehard Grünig (2)
  
  1. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany
  2. Centre of Pulmonary Hypertension Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, 69126, Heidelberg, Germany
  3. Unidad de Genética Médica, Servicio de Pediatría, Hospital Universitario Virgen de La Arrixaca, Murcia, Spain
  4. Department of Paediatric Cardiology, University of Heidelberg, Heidelberg, Germany
  5. Department of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum München, Technische Universit?t München, Munich, Germany
  6. German Heart Center, Berlin, Germany
  7. Department of Paediatric Cardiology, University of Giessen, Giessen, Germany
  

文摘

Background Aim of this prospective study was to compare clinical and genetic findings in children with idiopathic or heritable pulmonary arterial hypertension (I/HPAH) with children affected with congenital heart defects associated PAH (CHD-APAH). Methods Prospectively included were 40 consecutive children with invasively diagnosed I/HPAH or CHD-APAH and 117 relatives. Assessment of family members, pedigree analysis and systematic screening for mutations in TGF? genes were performed. Results Five mutations in the bone morphogenetic protein type II receptor (BMPR2) gene, 2 Activin A receptor type II-like kinase-1 (ACVRL1) mutations and one Endoglin (ENG) mutation were found in the 29 I/HPAH children. Two mutations in BMPR2 and one mutation in ACVRL1 and ENG, respectively, are described for the first time. In the 11 children with CHD-APAH one BMPR2 gene mutation and one Endoglin gene mutation were found. Clinical assessment of relatives revealed familial aggregation of the disease in 6 children with PAH (HPAH) and one CHD-APAH patient. Patients with mutations had a significantly lower PVR. Conclusion Mutations in different TGF? genes occurred in 8/29 (27.6%) I/HPAH patients and in 2/11 (18.2%) CHD-APAH patients and may influence the clinical status of the disease. Therefore, genetic analysis in children with PAH, especially in those with I/HPAH, may be of clinical relevance and shows the complexity of the genetic background.