Jing Zhi-cheng, Lu Li-he, Zou Yu-bao, You Shi-jie, Han Zhi-yan, Zhang Qian, Yang Yue-jin, Hui Ru-tai, Cheng Xian-sheng
Department of Internal Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Zhonghua Yi Xue Za Zhi. 2004 Feb 2;84(3):199-202.
To investigate the clinical and genetic characteristics of familial primary pulmonary hypertension (PPH) in Han nationality.
The clinical and laboratory features of patients of familial PPH in a family of Han nationality in Zhumadian, Henan Province, including the propositus, female, aged 37, her 29-years-old brother, and her 14-years-old daughter, were summarized. Samples of peripheral blood were collected from all family members and 100 healthy volunteers. Genomic DNA of the peripheral white blood cells was extracted from the samples. Primers for the exon 1 - 13 including the lateral intron of bone morphogenetic protein receptor-II (BMPR2) gene were designed. Then the genomic DNA was amplified by PCR. The PCR products were purified, sequenced, and compared with the sequence of normal BMPR2 gene.
The 3 patients in this family, coming down with the illness at the ages of 35, 23, and 13 respectively, suffered from severe pulmonary hypertension and cor pulmonale with the clinical manifestations of cough, hemoptysis, heart enlargement, and cardiac function of class III. The propositus' mother came down with PPH in the age of 42 and died 1 year later. Sequence analysis showed codon 491 C-->T conversion in exon 11 in all three patients (heterozygote), which induces arginine to change to tryptophan (R491W). None BMPR2 mutation was identified in the 100 normal controls and other family members without PPH.
As in the white people, the missense mutation of R491W in BMPR2 gene is also one crucial pathogenetic gene of familial PPH in Han nationality. There is no normal carrier of such genotype.
探讨汉族家族性原发性肺动脉高压（PPH）的临床及遗传学特征。
总结河南省驻马店市一个汉族家族中家族性PPH患者的临床及实验室特征，包括先证者，37岁女性，其29岁的弟弟和14岁的女儿。采集所有家庭成员及100名健康志愿者的外周血样本。从样本中提取外周血白细胞的基因组DNA。设计骨形态发生蛋白受体II（BMPR2）基因第1 - 13外显子包括侧翼内含子的引物。然后通过PCR扩增基因组DNA。对PCR产物进行纯化、测序，并与正常BMPR2基因序列进行比较。
该家族中的3例患者分别在35岁、23岁和13岁发病，患有严重的肺动脉高压和肺心病，临床表现为咳嗽、咯血、心脏扩大和心功能III级。先证者的母亲42岁患PPH，1年后死亡。序列分析显示，所有3例患者（杂合子）第11外显子密码子491发生C→T转换，导致精氨酸变为色氨酸（R491W）。在100名正常对照及其他无PPH的家族成员中未发现BMPR2突变。
与白种人一样，BMPR2基因R491W错义突变也是汉族家族性PPH的关键致病基因之一。不存在该基因型的正常携带者。
