title: Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension.
abstract: 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 TGFß 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.
  
  
  CONCLUSIONS
  Mutations in different TGFß 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.
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pfarr
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.forename: Nicola
authors.initials: N
authors.lastname: Ehlken
authors.forename: Tabea
authors.initials: T
authors.lastname: Becker-Grünig
authors.forename: Vanesa
authors.initials: V
authors.lastname: López-González
authors.forename: Matthias
authors.initials: M
authors.lastname: Gorenflo
authors.forename: Alfred
authors.initials: A
authors.lastname: Hager
authors.forename: Katrin
authors.initials: K
authors.lastname: Hinderhofer
authors.forename: Oliver
authors.initials: O
authors.lastname: Miera
authors.forename: Christian
authors.initials: C
authors.lastname: Nagel
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schranz
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Grünig
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D000071063:Endoglin; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D006439:Hemodynamics / Q000235:genetics*; D040941:Heredity; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000503:physiopathology*; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II