不同缺损大小先天性心脏病合并肺动脉高压患儿与BMPR2基因的临床观察

发布时间：2018-04-13 00:08

本文选题：小缺损型先天性心脏病 + 肺动脉高压　；参考：《华中科技大学》2016年硕士论文

【摘要】：目的:探讨不同缺损大小先天性心脏病患儿肺动脉高压的发生同BMPR2基因改变的关系。方法:收集自2014年3月20日至2014年10月20日在华中科技大学同济医学院附属协和医院7号手术室行心内直视术的50例先心病性肺动脉高压的患儿。根据超声心动图诊断心脏隔膜缺损面积分为大缺损组及小缺损组。分别抽取两组病例静脉血提取基因组DNA,PCR扩增BMPR2基因1-13号外显子并测序寻找变异点。结果:小缺损组发现1例复杂先天性心脏病合并重度肺动脉高压患儿BMPR2基因10号外显子发生G→T、G→A杂合子错义突变(c.1317 GT;c.1318 GA),该位置变异将会导致BMPR2基因编码的氨基酸发生改变,即:谷氨酸变为天冬氨酸、缬氨酸变为异亮氨酸,蛋白质空间结构也会随之发生构象改变。大缺损组未发现任何纯合子或杂合子有义突变。其次,共发现5例患儿发生BMPR2基因12号外显子1225位碱基发生GA的单核苷酸多肽性改变。其中小缺损组3例,大缺损组2例;重度肺动脉高压4例,轻度肺动脉高压1例。结论:1、BMPR2基因突变可能是小缺损型先天性心脏病合并肺动脉高压患儿的致病因素;2、携带BMPR2基因异常的先天性心脏病患儿易于发生重度肺动脉高压。
[Abstract]:Objective: to investigate the relationship between pulmonary hypertension and BMPR2 gene change in children with congenital heart disease with different defect sizes.Methods: from March 20, 2014 to October 20, 2014, 50 children with congenital heart disease with pulmonary hypertension were enrolled in the operation room 7 of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.According to echocardiography, the area of cardiac septum defect was divided into large defect group and small defect group.BMPR2 gene exon 1-13 was amplified by PCR from venous blood of two groups of patients and the mutation point was found by sequencing.Results: in the small defect group, a case of complex congenital heart disease complicated with severe pulmonary hypertension was found to have a missense mutation in the BMPR2 gene exon 10. The missense mutation of the heterozygote was identified as C. 1317 GTT / c. 1318 GAA. This mutation will lead to the coding of BMPR2 gene.Amino acid changes,That is, glutamic acid becomes aspartic acid, valine becomes isoleucine, and the spatial structure of protein also changes in conformation.No homozygous or heterozygous mutations were found in the large defect group.Secondly, a total of 5 children were found to have single nucleotide polypeptide changes of GA at the 1225 base of exon 12 of BMPR2 gene.There were 3 cases in small defect group, 2 cases in large defect group, 4 cases in severe pulmonary hypertension and 1 case in mild pulmonary hypertension.Conclusion the mutation of BMPR2 gene may be a pathogenic factor in children with small defect congenital heart disease complicated with pulmonary hypertension. Children with congenital heart disease with abnormal BMPR2 gene are prone to develop severe pulmonary hypertension.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R725.4

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