晶体连接蛋白基因突变导致遗传性先天性白内障的连锁定位和突变分析

发布时间：2018-02-26 16:11

本文关键词： 先天性白内障晶体连接蛋白基因突变分析　出处：《中国人民解放军医学院》2014年博士论文　论文类型：学位论文

【摘要】：研究背景和目的先天性白内障是一种重要的致盲因素,约占婴幼儿盲的大约三分之一。白内障在婴幼儿中的发病率为0.01-0.06%,大约一半的病例具有遗传性。随着人类基因组计划(Human Genome Project, HGP)的完成,促进了遗传性疾病基因的克隆。对于先天性遗传性白内障,已经报道了39个致病位点,克隆了其中的26个基因。丰富的先天性遗传性白内障的研究成果为人们认识白内障疾病的发生、发展提供了基础。但是由于遗传性先天性白内障基因型与临床表型的关系尚不明晰,因此需要通过对先天性遗传性白内障家系的进一步研究,来发现更多的新的基因和新的突变,从而研究致病基因与蛋白质的功能,以有助于阐明先天性遗传性白内障的致病机制,为疾病的防治奠定基础。材料与方法本研究主要针对临床诊断为先天性遗传性白内障,并有两代及两代以上、多人发病的常染色体显性遗传的先天性白内障家系为研究对象。2012年9月在江西收集到一个白内障家系。通过连锁分析和候选基因突变筛查的方法查找其致病基因。通过确定致病基因来研究先天性白内障的致病机制。结果在这个白内障家系中,连锁分析检测到GJA8(connexin50)的变异与家系的白内障遗传高度相关。家系中对患者的DNA直接测序发现在GJA8的exonl的第145位碱基由C突变为G,结果导致第49位氨基酸由谷氨酰胺变为谷氨酸。结论本研究发现在这个白内障家系中患者的DNA直接测序发现在GJA8的exonl的第145位碱基由C突变为G。这是这个致病基因的目前尚未报道的新的突变位
[Abstract]:Background and purpose of the study. Congenital cataract is an important cause of blindness, accounting for about 1/3 of infantile blindness. The incidence of cataract in infants is 0.01-0.06, about half of the cases are hereditary. With the completion of Human Genome Project (HGP), the gene cloning of hereditary diseases has been promoted. For congenital hereditary cataract, 39 pathogenic sites have been reported and 26 of them have been cloned. The abundant research results of congenital hereditary cataract provide a basis for people to understand the occurrence and development of cataract. However, the relationship between genotypes and clinical phenotypes of inherited congenital cataract is still unclear. Therefore, it is necessary to find more new genes and new mutations through further study of the pedigrees of congenital hereditary cataract, so as to study the function of pathogenic genes and proteins. In order to help clarify the pathogenesis of congenital hereditary cataract and lay the foundation for the prevention and treatment of disease. Materials and methods. This study is aimed at clinical diagnosis of congenital hereditary cataract, and has two or more generations. In September 2012, an autosomal dominant congenital cataract family was collected in Jiangxi province. Linkage analysis and screening of candidate gene mutation were used to find its pathogenic gene. To study the pathogenetic mechanism of congenital cataract by identifying the pathogenic gene. In this cataract family, Linkage analysis showed that the variation of GJA8 connexin 50) was highly correlated with the pedigrees' cataract heredity. Direct sequencing of the patient's DNA in the pedigree revealed that the 145th base of exonl in GJA8 mutated from C to G, resulting in the 49th amino acid from glutamine. Become glutamic acid. Conclusion. In this study, we found that the direct sequencing of the DNA of the patient in this pedigrees with cataract revealed that the 145th base mutation in the exonl of GJA8 was changed from C to G. this is a new mutation of this pathogenic gene that has not been reported yet.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R776.1

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