目的:通过研究中国汉族法洛四联症(tetralogy of Fallot,TOF)患儿心肌中GATA6、TBX20基因的表达变化,初步探讨GATA6、TBX20基因与汉族TOF分子发病机制之间的关系。方法:实验组选取中国汉族TOF患儿15例,年龄6.5个月～8岁,平均1.9岁,术中...目的:通过研究中国汉族法洛四联症(tetralogy of Fallot,TOF)患儿心肌中GATA6、TBX20基因的表达变化,初步探讨GATA6、TBX20基因与汉族TOF分子发病机制之间的关系。方法:实验组选取中国汉族TOF患儿15例,年龄6.5个月～8岁,平均1.9岁,术中常规切除并留取右心室流出道肥厚心肌;对照组选取汉族室间隔缺损患儿15例,年龄4.5个月～5岁,平均2.2岁。术中留取患儿右心房壁少量心肌组织。提取心肌组织RNA,应用实时荧光聚合酶链反应检测两组心肌中的GATA6、TBX20基因mRNA表达;应用免疫组化染色技术,检测两组心肌中的GATA6、TBX20蛋白的表达并进行统计学比较分析。结果:TOF患者心肌中GATA6、TBX20基因mRNA和蛋白表达水平均较对照组显著降低,差异有统计学意义;同时,TOF患儿心肌TBX20mRNA水平与患儿肺动脉指数呈正相关(r=0.6782,P<0.05)。结论:人类心肌中存在GATA6、TBX20mRNA和蛋白的表达;在中国汉族人群中,TOF的发生可能与心肌组织中GATA6、TBX20基因表达下调有关。展开更多
Congenital heart disease （CHD） is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect （ASD） is one of the most common defects of CHD. Previous studies have demon...Congenital heart disease （CHD） is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect （ASD） is one of the most common defects of CHD. Previous studies have demonstrated that mutations in the transcription factor T-box 20 （TBX20） contribute to congenital ASD. Whole-exome sequencing in combination with a CHD-related gene filter was used to detect a family of three generations with ASD. A novel TBX20 mutation, c.526G〉A （p.D176N）, was identified and co-segregated in all affected members in this family. This mutation was predicted to be deleterious by bioinformatics programs （SIFT, Polyphen2, and MutationTaster）. This mutation was also not presented in the current Single Nucleotide Polymorphism Database （dbSNP） or National Heart, Lung, and Blood Institute （NHLBI） Exome Sequencing Project （ESP）. In conclusion, our finding expands the spectrum of TBX20 mutations and provides additional support that TBX20 plays important roles in cardiac development. Our study also provided a new and cost-effective analysis strategy for the genetic study in small CHD pedigree.展开更多
文摘目的:通过研究中国汉族法洛四联症(tetralogy of Fallot,TOF)患儿心肌中GATA6、TBX20基因的表达变化,初步探讨GATA6、TBX20基因与汉族TOF分子发病机制之间的关系。方法:实验组选取中国汉族TOF患儿15例,年龄6.5个月～8岁,平均1.9岁,术中常规切除并留取右心室流出道肥厚心肌;对照组选取汉族室间隔缺损患儿15例,年龄4.5个月～5岁,平均2.2岁。术中留取患儿右心房壁少量心肌组织。提取心肌组织RNA,应用实时荧光聚合酶链反应检测两组心肌中的GATA6、TBX20基因mRNA表达;应用免疫组化染色技术,检测两组心肌中的GATA6、TBX20蛋白的表达并进行统计学比较分析。结果:TOF患者心肌中GATA6、TBX20基因mRNA和蛋白表达水平均较对照组显著降低,差异有统计学意义;同时,TOF患儿心肌TBX20mRNA水平与患儿肺动脉指数呈正相关(r=0.6782,P<0.05)。结论:人类心肌中存在GATA6、TBX20mRNA和蛋白的表达;在中国汉族人群中,TOF的发生可能与心肌组织中GATA6、TBX20基因表达下调有关。
基金Project supported by the National Natural Science Foundation of China （Nos. 81370204, 81300072, and 81101475） Electronic supplementary materials： The online version of this article （htlp：//dx.doi.org/10.1631/jzus.B1400062） contains supplementary materials, which are available to authorized users
文摘Congenital heart disease （CHD） is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect （ASD） is one of the most common defects of CHD. Previous studies have demonstrated that mutations in the transcription factor T-box 20 （TBX20） contribute to congenital ASD. Whole-exome sequencing in combination with a CHD-related gene filter was used to detect a family of three generations with ASD. A novel TBX20 mutation, c.526G〉A （p.D176N）, was identified and co-segregated in all affected members in this family. This mutation was predicted to be deleterious by bioinformatics programs （SIFT, Polyphen2, and MutationTaster）. This mutation was also not presented in the current Single Nucleotide Polymorphism Database （dbSNP） or National Heart, Lung, and Blood Institute （NHLBI） Exome Sequencing Project （ESP）. In conclusion, our finding expands the spectrum of TBX20 mutations and provides additional support that TBX20 plays important roles in cardiac development. Our study also provided a new and cost-effective analysis strategy for the genetic study in small CHD pedigree.
