Background: Aim of this prospective study was to compare clinical and genetic findings in children with idiopathic\r\nor heritable pulmonary arterial hypertension (I/HPAH) with children affected with congenital heart defects\r\nassociated PAH (CHD-APAH).\r\nMethods: Prospectively included were 40 consecutive children with invasively diagnosed I/HPAH or CHD-APAH\r\nand 117 relatives. Assessment of family members, pedigree analysis and systematic screening for mutations in TGF�Ÿ\r\ngenes were performed.\r\nResults: Five mutations in the bone morphogenetic protein type II receptor (BMPR2) gene, 2 Activin A receptor\r\ntype II-like kinase-1 (ACVRL1) mutations and one Endoglin (ENG) mutation were found in the 29 I/HPAH children.\r\nTwo mutations in BMPR2 and one mutation in ACVRL1 and ENG, respectively, are described for the first time. In the\r\n11 children with CHD-APAH one BMPR2 gene mutation and one Endoglin gene mutation were found. Clinical\r\nassessment of relatives revealed familial aggregation of the disease in 6 children with PAH (HPAH) and one\r\nCHD-APAH patient. Patients with mutations had a significantly lower PVR.\r\nConclusion: Mutations in different TGF�Ÿ genes occurred in 8/29 (27.6%) I/HPAH patients and in 2/11 (18.2%)\r\nCHD-APAH patients and may influence the clinical status of the disease. Therefore, genetic analysis in children with\r\nPAH, especially in those with I/HPAH, may be of clinical relevance and shows the complexity of the genetic\r\nbackground.
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