遗传性对称性色素异常症的ADAR1基因突变研究

发布时间：2018-06-22 16:35

本文选题：遗传性对称性色素异常症 + ADAR1基因　；参考：《川北医学院》2016年硕士论文

【摘要】：研究背景:遗传性对称性色素异常症(Dyschromatosis symmetrica hereditaria,DSH,OMIM127400),是一种临床上较少见的常染色体显性遗传性皮肤病。主要表现为四肢末端对称性分布的色素沉着和色素减退斑,形成网状图案,尤以手、足背部较明显,可伴面部散在雀斑样斑点。DSH的致病基因已明确为ADAR1基因,其定位于1号染色体长臂21.3区带,编码双链RNA特异性腺苷脱氨基酶,该酶属于RNA编辑酶,能够选择性作用于mRNA前体,并可将mRNA特殊位点上的腺嘌呤核苷去氨基转变为次黄嘌呤核苷,形成新的剪切位点或密码子,结果引起该蛋白功能的改变。近年来,ADAR1基因新的突变不断被报道,不仅丰富了ADAR1基因突变谱,而且为进一步研究基因型与表型的关系,以及DSH发病的分子遗传学机制奠定基础。目的:检测遗传性对称性色素异常症2个家系和1例散发病例的ADAR1基因突变情况。方法:收集中国四川汉族人2个DSH家系及1例散发病例的临床资料,提取患者及其家庭成员外周静脉血DNA,采用聚合酶链反应(Polymerase chain reaction,PCR)扩增ADAR1基因所有外显子编码区及其侧翼序列,并采用PCR扩增产物直接测序的方法进行ADAR1基因突变检测。结果:DSH家系1患者ADAR1基因第8外显子存在c.2638delG(p.Asp880ThrfsX15)移码突变;家系2患者ADAR1基因第12外显子发现c.3109AG(p.S1037G)错义突变;DSH散发病例ADAR1基因第10外显子存在c.2867CA(p.S956X)无义突变,以上三个突变未见报道,均为新突变。在相应表型正常的家庭成员及100名无亲缘关系的正常个体中均未检测出上述三个突变。结论:ADAR1基因移码突变c.2638delG(p.Asp880ThrfsX15)、错义突变c.3109AG(p.S1037G)和无义突变c.2867CA(p.S956X)可能分别是DSH家系1、家系2及散发病例发病的原因。
[Abstract]:Background: Dyschromatosis Symmetrica hereditaria (DSH, OMIM127400). It is a rare autosomal dominant hereditary dermatosis in clinic. It is characterized by pigmentation and pigmentation in the symmetrical distribution of extremities, forming a reticular pattern, especially in the hand, and in the back of the foot. The pathogenetic gene of the freckled spot.DSH has been identified as the ADAR1 gene, which is located at the 21.3 zone of the long arm of chromosome 1 and encodes a double stranded RNA specific adenosine deaminase, which belongs to the RNA editing enzyme, which can selectively act on the precursor of the mRNA and transform the adenosine deaminase on the special loci of mRNA to the hypoxanthine nucleoside. New shear loci or codons are formed, resulting in a change in the function of the protein. In recent years, new mutations in the ADAR1 gene have been reported, which not only enriches the mutation spectrum of the ADAR1 gene, but also provides a basis for further study of the relationship between genotype and phenotype as well as the molecular genetic mechanism of DSH. Objective: to detect hereditary symmetry color. ADAR1 gene mutation in 2 families and 1 sporadic cases of vegetal disorder. Methods: the clinical data of 2 DSH families and 1 sporadic cases of Sichuan Han people in China were collected. The peripheral venous blood DNA of the patients and their family members was extracted and all the exon coding regions of the ADAR1 gene were amplified by polymerase chain reaction (PCR) and the encoding area of all the exons of the ADAR1 gene was amplified. The ADAR1 gene mutation was detected by the direct sequencing of the PCR amplification products. The results showed that the ADAR1 gene eighth exon of the DSH family 1 had c.2638delG (p.Asp880ThrfsX15) code shift mutation; the twelfth exon of the ADAR1 gene of the family 2 patients found the c.3109AG (p.S1037G) missense mutation; DSH sporadic case ADAR1 gene tenth exits. There was a c.2867CA (p.S956X) nonsense mutation. The above three mutations were not reported, all of which were new mutations. The above three mutations were not detected in the normal family members and 100 unrelated normal individuals in the corresponding phenotypes. Conclusion: ADAR1 gene shift mutation c.2638delG (p.Asp880ThrfsX15), missense mutation c.3109AG (p.S1037G) and unsense process The change of c.2867CA (p.S956X) may be caused by DSH family 1, family 2 and sporadic cases.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R758.5

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