Implications of mutations of activin receptor-like kinase 1 gene (ALK1) in addition to bone morphogenetic protein receptor II gene (BMPR2) in children with pulmonary arterial hypertension
Implications of mutations of activin receptor-like kinase 1 gene (ALK1) in addition to bone morphogenetic protein receptor II gene (BMPR2) in children with pulmonary arterial hypertension
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DOI：
10.1253/circj.72.127
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Saji, Tsutomu
中科院分区：
文献类型：
--
作者：
Fujiwara, Maya;Yagi, Hisato;Saji, Tsutomu
背景 肺动脉高压（PAH）患者中已有骨形态发生蛋白受体 R 基因（BMPR2）突变和激活素受体样激酶 I 基因（ALK1）1 种突变的报道。 方法和结果 对 21 名 16 岁以下 PAH 先证者进行 ALK1 和 BMPR2 基因组研究，以研究患者临床特征与这些特征之间的关系。 基因。在所有 4 个 PAH 家族聚集体中，鉴定出 3 个 ALK1 或 1 个 BMPR2 突变。在17名年龄在4岁至14岁之间的特发性PAH先证者中，发现2个ALK1突变（2/17：11.8％）和3个BMPR2突变（3/17：17.6％；总共5个突变：5/17：29.4％）。结论每个具有ALK1突变的先证者都发展为PAH，具有BMPR2突变的先证者也是如此。因此，有人提出 ALK1 在 PAH 病因学中与 BMPR2 一样发挥着重要作用。此外，丝氨酸-苏氨酸激酶结构域内有 ALK1 突变的无症状携带者有患 PAH 和遗传性出血性毛细血管扩张症的风险，因此建议对这些个体进行密切随访。
Background Mutations of the bone morphogenetic protein receptor R gene (BMPR2), and 1 mutation of the activin receptor-like kinase I gene (ALK1) have been reported in patients with pulmonary arterial hypertension (PAH).Methods and Results A genomic study of ALK1 and BMPR2 was conducted in 21 PAH probands under 16 years of age to study the relationship between the clinical features of the patients and these genes. In all 4 familial aggregates of PAH, 3 ALK1 or I BMPR2 mutations were identified. Among 17 probands aged between 4 and 14 years with idiopathic PAH, 2 ALK1 mutations (2/17: 11.8%) and 3 BMPR2 mutations (3/17: 17.6%; 5 mutations in total: 5/17: 29.4%) were found.Conclusion Each proband with the ALK1 mutation developed PAH, as did the probands with the BMPR2 mutation. Hence, it is proposed that ALK1 plays as notable a role as BMPR2 in the etiology of PAH. Furthermore, asymptomatic carriers with the ALK1 mutation within the serine-threonine kinase domain are at risk of developing PAH and hereditary hemorrhagic telangiectasia, so close follow-up is recommended for those individuals.