BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease
BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease
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DOI：
10.1183/09031936.04.00018604
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发表时间：
2004-09-01
影响因子：
24.3
通讯作者：
Morse, JH
中科院分区：
文献类型：
--
作者：
Roberts, KE;McElroy, JJ;Morse, JH
本研究的目的是确定肺血管阻塞性疾病所致肺动脉高压（PAH）和先天性心脏病（CHD）患者编码骨形态发生蛋白受体（BMPR）-2的基因是否存在突变。CHD包括动脉导管未闭、房间隔缺损和室间隔缺损、部分肺静脉回流异常、大动脉转位、房室管和罕见的体肺分流病变。在四分之三的完全C型房室管成人和三名儿童中发现了六种新的BMPR 2错义突变。一个孩子有房间隔缺损和动脉导管未闭;一个有房间隔缺损，动脉导管未闭和部分异常肺静脉回流;和一个有肺动脉高压窗和室间隔缺损。骨形态发生蛋白受体2突变被发现在6%的成人和儿童混合队列的肺动脉高压/先天性心脏病。目前的研究结果补充了最近在小鼠模型中的报告，涉及骨形态发生蛋白/转化生长因子β途径的成员诱导类似于人类房室管，间隔缺损和圆锥动脉干先天性心脏病的心脏畸形。研究的患者数量较少，以及选择肺动脉高压时固有的确定偏倚需要进一步研究。
The aim of the present study was to determine if patients with both pulmonary arterial hypertension (PAH), due to pulmonary vascular obstructive disease, and congenital heart defects (CHD), have mutations in the gene encoding bone morphogenetic protein receptor (BMPR)-2.The BMPR2 gene was screened in two cohorts: 40 adults and 66 children with PAH/CHD. CHDs were patent ductus arteriosus, atrial and ventricular septal defects, partial anomalous pulmonary venous return, transposition of the great arteries, atrioventicular canal, and rare lesions with systemic-to-pulmonary shunts.Six novel missense BMPR2 mutations were found in three out of four adults with complete type C atrioventricular canals and in three children. One child had an atrial septal defect and patent ductus arteriosus; one had an atrial septal defect, patent ductus arteriosus and partial anomalous pulmonary venous return; and one had an aortopulmonary window and a ventricular septal defect.Bone morphogenetic protein receptor 2 mutations were found in 6% of a mixed cohort of adults and children with pulmonary arterial hypertension/congenital heart defects. The current findings compliment recent reports in mouse models implicating members of the bone morphogenetic protein/transforming growth factor-beta pathway inducing cardiac anomalies analogous to human atrioventricular canals, septal defects and conotruncal congenital heart defects. The small number of patients studied and the ascertainment bias inherent in selecting for pulmonary arterial hypertension require further investigation.