Primary pulmonary hypertension in children may have a different genetic background than in adults
Primary pulmonary hypertension in children may have a different genetic background than in adults
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DOI：
10.1203/01.pdr.0000139481.20847.d0
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发表时间：
2004-10-01
影响因子：
3.6
通讯作者：
Janssen, B
中科院分区：
文献类型：
--
作者：
Grünig, E;Koehler, R;Janssen, B
2q33染色体上的骨形态发生蛋白受体II （BMPR2）基因突变可引起家族性原发性肺动脉高压（PPH）， 26%的散发性成人患者可能发生这种突变。其他疾病相关基因已定位于染色体2q31 （PPH2）和12q13 （ALK1）。受影响儿童的遗传背景尚不清楚。采用变性高效液相色谱法和序列分析对13名确诊PPH的患儿（诊断时年龄6个月至13岁，平均5.6±3.9岁）进行BMPR2突变筛查。此外，通过Southern blot分析对所有儿童进行BMPR2缺失扫描。对6名婴儿的57名家庭成员在休息和运动时的肺动脉压进行了超声心动图评估。对6个家族进行连锁分析。13名儿童中没有BMPR2突变或缺失。与2号或12号染色体的连锁在所有被调查的家族中均未被证实。在所有被评估的家庭中，指数患者的父母和/或两个分支的成员都表现出对运动的异常肺动脉收缩压（PASP）反应。儿童PPH的遗传背景可能与成人不同。我们假设在一定比例的婴儿病例中存在隐性遗传模式。
Mutations of the bone morphogenetic protein receptor II (BMPR2) gene on chromosome 2q33 can cause familial primary pulmonary hypertension (PPH) and may occur in 26% adult patients with sporadic disease. Other disease-related genes have been localized to chromosomes 2q31 (PPH2) and 12q13 (ALK1). The genetic background in affected children remains unclear. Thirteen children (age at diagnosis, 6 mo to 13 y; mean, 5.6 +/- 3.9 y) with invasively confirmed PPH were screened for BMPR2 mutations using denaturing HPLC and sequence analysis. In addition, all children were scanned for BMPR2 deletions by Southern blot analysis. Pulmonary artery pressure was assessed using echocardiography at rest and during exercise in 57 family members of six infants. The six families were subjected to linkage analysis. None of the 13 children had a BMPR2 mutation or deletion. Linkage to chromosome 2 or 12 could not be confirmed in any of the families investigated. In all assessed families, both parents of the index patient and/or members of both branches revealed an abnormal pulmonary artery systolic pressure (PASP)-response to exercise. PPH in children may have a different genetic background than in adults. We postulate a recessive mode of inheritance in a proportion of infantile cases.