Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension.
Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension.
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DOI：
10.1186/1465-9921-14-3
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发表时间：
2013-01-09
影响因子：
5.8
通讯作者：
Grünig E
中科院分区：
文献类型：
--
作者：
Pfarr N;Fischer C;Ehlken N;Becker-Grünig T;López-González V;Gorenflo M;Hager A;Hinderhofer K;Miera O;Nagel C;Schranz D;Grünig E
本前瞻性研究的目的是比较特发性或遗传性肺动脉高压（I/HPAH）儿童与先天性心脏病相关PAH（CHD-APAH）儿童的临床和遗传学结果。主要包括40名连续的儿童与侵入性诊断I/HPAH或CHD-APAH和117亲属。对家系成员进行评估、家系分析和系统筛查TGF β基因突变。在29例I/HPAH患儿中发现5例骨形态发生蛋白II型受体（BMPR 2）基因突变，2例激活素A受体II型样激酶1（ACVRL 1）基因突变和1例内皮糖蛋白（ENG）基因突变。两个突变BMPR 2和一个突变ACVRL 1和ENG，分别是第一次被描述。在11例CHD-APAH患儿中发现1例BMPR 2基因突变和1例Endoglin基因突变，6例PAH患儿（HPAH）和1例CHD-APAH患儿的亲属中发现该病有家族聚集性。突变患者的PVR显著降低。I/HPAH患者中8/29例（27.6%）和CHD-APAH患者中2/11例（18.2%）发生不同TGF β基因突变，可能影响疾病的临床状态。因此，PAH儿童，特别是I/HPAH儿童的遗传分析可能具有临床相关性，并显示遗传背景的复杂性。
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). 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. 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. 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.
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影响因子：
3.6
作者：
Grünig, E;Koehler, R;Janssen, B
通讯作者：
Janssen, B
影响因子：
168.9
作者：
Berger, Rolf M. F.;Beghetti, Maurice;Humpl, Tilman;Raskob, Gary E.;Ivy, D. Dunbar;Jing, Zhi-Cheng;Bonnet, Damien;Schulze-Neick, Ingram;Barst, Robyn J.
通讯作者：
Barst, Robyn J.
影响因子：
3.9
作者：
Aldred, Micheala A.;Vijayakrishnan, Jairam;Trembath, Richard C.
通讯作者：
Trembath, Richard C.
影响因子：
3.3
作者：
Fujiwara, Maya;Yagi, Hisato;Saji, Tsutomu
通讯作者：
Saji, Tsutomu
影响因子：
2.3
作者：
Hill, Kevin D.;Lim, D. Scott;Everett, Allen D.;Ivy, D. Dunbar;Moore, J. Donald
通讯作者：
Moore, J. Donald