先天性心脏病并肺动脉高压患儿骨形成蛋白Ⅱ型受体基因新突变  

A Novel Mutation in Bone Morphogenetic Protein Receptor Ⅱ Gene in Children with Congenital Heart Disease Combined with Pulmonary Arterial Hypertension

作　　者：魏美丽[1] 韩波[1] 王来城[2] 孙瑾[1] 

机构地区：[1]山东大学附属省立医院小儿心脏科,济南250021 [2]山东大学附属省立医院中心实验室,济南250021

出　　处：《实用儿科临床杂志》2012年第13期994-996,999,共4页Journal of Applied Clinical Pediatrics

摘　　要：目的探讨骨形成蛋白Ⅱ型受体(BMPR2)基因外显子突变与先天性心脏病并肺动脉高压(CHD/PAH)之间的关系。方法收集66例无血缘关系的CHD/PAH患儿。均为汉族;男39例,女27例;VSD 25例,复杂CHD 20例,PDH 16例,ASD 5例。另收集66例健康儿童作为健康对照组。采集所有对象外周静脉血,提取基因组DNA,PCR方法扩增BMPR2基因的13个外显子编码序列后,对扩增产物纯化后进行测序,测序峰图用Sequencher 4.7 Demo软件进行分析,与GenBank人BMPR2的基因序列进行比对。结果 1.病例组检出1例部分性房室隔缺损并二尖瓣前叶裂、PAH患儿BMPR2基因外显子8发生错义突变,经数据库查对,该突变为一新的突变位点,而其余病例与健康对照组均未发现相同位点发生碱基突变;2.病例组9例和健康对照组10例儿童BMPR2基因编码区有一单核苷酸多态位点,即c.2811G>A,2组间差异无统计学意义。结论在我国汉族CHD/PAH患儿中首次发现BMPR2基因外显子8发生错义突变,该新的错义突变可能与CHD并PAH形成有关。Objective To determine if patients with congenital heart disease and pulmonary arterial hypertension （ CHD/PAH ） have mutations in the gene encoding bone morphogenetic protein receptor Ⅱ （BMPR2）. Methods Sixty - six children with CHD/PAH were re- cruited. There was no consanguineous relationship among them. All patients belonged to the Han nationality ：39 cases were male and 27 cases were female. Among them,25 patients had ventricular septal defect （VSD） ,20 patients had complicated CHD, 16 patients had patent ductus arteriosus （PDA） ,5 patients had atrial septal defect （ASD）. Sixty - six matched healthy controls were collected too. The entire protein - cod- ing region and intron/exon boundaries of BMPR2 gene were amplified by polymerase chain reaction（PCR） using DNA samples from all pa- tients and healthy controls. The PCR products were purified and sequenced. Peak charts of sequencing were analyzed with Sequencher 4.7 Demo software and compared with sequence of BMPR2 gene in GenBank. Results 1. A novel missense mutation, a G - to - A transition at position 1 042 in exon 8, which encodes a Val 348 Ile mutation, of the BMPR2 gene, was identified in a female pediatric patient with partial at- rioventricular septal defect/anterior mitral valve cleft/pulmonary arterial hypertension （PAVSD/AMVC/PAH）. None BMPR2 mutation was i- dentified in the 66 healthy controls and other patients with CHD/ PAH. 2. A single nucleotide polymorphisms （ SNP）, c. 2811G 〉 A, in the BMPR2 gene was identified in 9 patients and 10 controls. However, no significant difference was found in the frequency distribution of the SNP between patients with CHD/PAH and healthy controls. Conclusions A missense mutation in exon 8 of BMPR2 gene was first discovered in patients with CHD/PAH. The new missense mutation may be responsible for the development of CHD/PAH.

关 键 词：先天性心脏病 肺动脉高压 骨形成蛋白Ⅱ型受体 基因 突变 

分 类 号：R725.4[医药卫生—儿科]