本文選題：全基因組比較雜交芯片（aCGH） + GATA4　； 參考：《哈爾濱醫(yī)科大學》2012年博士論文

【摘要】：背景GATA4是調(diào)控心肌細胞分化和功能的關鍵性基因，其單倍劑量不足與先天性心臟病（congenital heart defects，，CHD)關系密切。然而目前對GATA4的重復是否能夠?qū)е翪HD卻不明確。 方法我們采用高分辨率芯片比較基因組雜交（comparative genomichybridization， aCGH)的方法連續(xù)對1645個患有各種發(fā)育異常的兒童患者進行檢測。 結果我們檢測到8名患兒和兩名家長攜帶有含有GATA4的病原性基因組失衡。其中4名患兒帶有一個~4.0Mb的節(jié)段性重復，該節(jié)段位于兩個嗅覺感受器基因簇(REPD和REPP)之間，約占被檢測患者總數(shù)的0.24%(4/1645)。這4個患兒都沒有CHD或其它心臟疾病，只是其中一名患兒的母親有主動脈瓣狹窄的病史，是她將該變異遺傳給她的孩子的。兩名攜帶有包括GATA4重復在內(nèi)的多基因組異常的患兒患有復雜的CHD。在另外3個帶有GATA4缺失的患兒中，只有1人患有房間隔缺損（atrial septal defects，ASD)和室間隔缺損（ventricular septaldefect，VSD)。 結論1.心臟缺陷在攜帶包括GATA4在內(nèi)的8p23.1基因組重復的患者中是少見的。在我們的研究中，該重復的0.24%的檢出率顯著高于以前估計的結果。2.我們在兩個患有多種遺傳缺陷和復雜先天性心臟病的患者觀察到的情況與一種叫做“二次打擊模型”理論相符，該理論強調(diào)對基因組的多種損害累加的效果可以導致可見的或更加嚴重的臨床表現(xiàn)。3.GATA4的單倍缺失可以表現(xiàn)為包括先天性心臟病在內(nèi)的多種臨床表現(xiàn)。
[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.

【學位授予單位】：哈爾濱醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R725.4

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