Zhicheng Jing, Lihe Lu, Zhiyan Han, Xiansheng Cheng, Yubao Zou, Yuejin Yang, Rutai Hui
Department of Cardiololgy, Fu Wai Heart Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No.167 Beilishilu, Beijing 100037, China.
Biochem Biophys Res Commun. 2004 Mar 19;315(4):1033-8. doi: 10.1016/j.bbrc.2004.01.158.
A four-generation pedigree of familial primary pulmonary hypertension (FPPH) with 14 alive members was collected. In the family, three of the 14 alive familial members were diagnosed as FPPH. Mutations in bone morphogenetic protein receptor-II (BMPR-II) gene were screened by using sequencing analysis. A C-to-T transition at position 1471 in exon 11 of the BMPR-II gene was identified, resulting in an Arg491Trp mutation. We confirmed segregation of the mutation within the family and excluded the presence of the mutations in a panel of 240 chromosomes from normal individuals. No mutations were found in BMPR-II gene in other 10 patients with sporadic primary pulmonary hypertension. The Arg491Trp mutation is located in the kinase domain and predicted to disturb the kinase activity of BMPR-II. Total 7 familial members died at age 8-45 years with various symptoms, indicating other genetic or environmental modifiers involved in the modification of the clinical phenotype.
收集了一个有14名在世成员的家族性原发性肺动脉高压（FPPH）四代家系。在这个家族中，14名在世家族成员中有3人被诊断为FPPH。通过测序分析筛查骨形态发生蛋白受体II（BMPR-II）基因的突变。在BMPR-II基因第11外显子的1471位发现了一个C到T的转换，导致了Arg491Trp突变。我们证实了该突变在家族中的分离，并在来自正常个体的240条染色体中排除了该突变的存在。在其他10例散发性原发性肺动脉高压患者中未发现BMPR-II基因的突变。Arg491Trp突变位于激酶结构域，预计会干扰BMPR-II的激酶活性。共有7名家族成员在8至45岁时因各种症状死亡，表明其他基因或环境修饰因子参与了临床表型的改变。
