心脏缺陷少见于携带包括GATA4在内的8p23.1基因组重复的患者

发布时间：2018-04-14 11:14

本文选题：全基因组比较杂交芯片（aCGH） + GATA4　；参考：《哈尔滨医科大学》2012年博士论文

【摘要】：背景GATA4是调控心肌细胞分化和功能的关键性基因，其单倍剂量不足与先天性心脏病（congenital heart defects，，CHD)关系密切。然而目前对GATA4的重复是否能够导致CHD却不明确。方法我们采用高分辨率芯片比较基因组杂交（comparative genomichybridization， aCGH)的方法连续对1645个患有各种发育异常的儿童患者进行检测。结果我们检测到8名患儿和两名家长携带有含有GATA4的病原性基因组失衡。其中4名患儿带有一个~4.0Mb的节段性重复，该节段位于两个嗅觉感受器基因簇(REPD和REPP)之间，约占被检测患者总数的0.24%(4/1645)。这4个患儿都没有CHD或其它心脏疾病，只是其中一名患儿的母亲有主动脉瓣狭窄的病史，是她将该变异遗传给她的孩子的。两名携带有包括GATA4重复在内的多基因组异常的患儿患有复杂的CHD。在另外3个带有GATA4缺失的患儿中，只有1人患有房间隔缺损（atrial septal defects，ASD)和室间隔缺损（ventricular septaldefect，VSD)。结论1.心脏缺陷在携带包括GATA4在内的8p23.1基因组重复的患者中是少见的。在我们的研究中，该重复的0.24%的检出率显著高于以前估计的结果。2.我们在两个患有多种遗传缺陷和复杂先天性心脏病的患者观察到的情况与一种叫做“二次打击模型”理论相符，该理论强调对基因组的多种损害累加的效果可以导致可见的或更加严重的临床表现。3.GATA4的单倍缺失可以表现为包括先天性心脏病在内的多种临床表现。
[Abstract]:Background GATA4 is a key gene regulating cardiomyocyte differentiation and function. Its haploinsufficiency is closely related to congenital heart defects (CHD). However, it is not clear whether GATA4 repeats can induce CHD at present.
Methods we used high-resolution comparative genomichybridization (aCGH) to detect 1645 children with various developmental abnormalities.
Results we detected 8 children and two parents carry pathogenic genomic imbalances containing GATA4. Segmental duplications among 4 children with a ~4.0Mb, the segment is located in the two olfactory receptor gene clusters (REPD and REPP), accounting for about 0.24% of the total number of patients was detected (4/1645) of the 4 children. No CHD or other heart disease, is one of the mothers with aortic stenosis is the history of her genetic variation to her children. Two with GATA4 repeat, including multiple genome abnormal patients with complex CHD. in the other 3 with GATA4 deletion children, only 1 people with ASD (atrial septal defects, ASD) and ventricular septal defect (ventricular, septaldefect, VSD).
Conclusion the 1. heart defects in carrying GATA4 including 8p23.1 genome duplication in patients is rare. In our study, the detection rate of repeat 0.24% was significantly higher than that of the previously estimated results.2. us in two with a variety of genetic defects and complex congenital heart disease were observed with a call the "two hit model" is consistent with the theory, this theory emphasizes the effect of a variety of damage to the genome accumulation can lead to visible or more severe clinical manifestations of.3.GATA4 single deletion can be represented as a variety of clinical manifestations including congenital heart disease.

【学位授予单位】：哈尔滨医科大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R725.4

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