本文選題：遺傳性對稱性色素異常癥 + ADAR1基因　； 參考：《川北醫(yī)學(xué)院》2016年碩士論文

【摘要】：研究背景:遺傳性對稱性色素異常癥(Dyschromatosis symmetrica hereditaria,DSH,OMIM127400),是一種臨床上較少見的常染色體顯性遺傳性皮膚病。主要表現(xiàn)為四肢末端對稱性分布的色素沉著和色素減退斑,形成網(wǎng)狀圖案,尤以手、足背部較明顯,可伴面部散在雀斑樣斑點(diǎn)。DSH的致病基因已明確為ADAR1基因,其定位于1號染色體長臂21.3區(qū)帶,編碼雙鏈RNA特異性腺苷脫氨基酶,該酶屬于RNA編輯酶,能夠選擇性作用于mRNA前體,并可將mRNA特殊位點(diǎn)上的腺嘌呤核苷去氨基轉(zhuǎn)變?yōu)榇吸S嘌呤核苷,形成新的剪切位點(diǎn)或密碼子,結(jié)果引起該蛋白功能的改變。近年來,ADAR1基因新的突變不斷被報(bào)道,不僅豐富了ADAR1基因突變譜,而且為進(jìn)一步研究基因型與表型的關(guān)系,以及DSH發(fā)病的分子遺傳學(xué)機(jī)制奠定基礎(chǔ)。目的:檢測遺傳性對稱性色素異常癥2個家系和1例散發(fā)病例的ADAR1基因突變情況。方法:收集中國四川漢族人2個DSH家系及1例散發(fā)病例的臨床資料,提取患者及其家庭成員外周靜脈血DNA,采用聚合酶鏈反應(yīng)(Polymerase chain reaction,PCR)擴(kuò)增ADAR1基因所有外顯子編碼區(qū)及其側(cè)翼序列,并采用PCR擴(kuò)增產(chǎn)物直接測序的方法進(jìn)行ADAR1基因突變檢測。結(jié)果:DSH家系1患者ADAR1基因第8外顯子存在c.2638delG(p.Asp880ThrfsX15)移碼突變;家系2患者ADAR1基因第12外顯子發(fā)現(xiàn)c.3109AG(p.S1037G)錯義突變;DSH散發(fā)病例ADAR1基因第10外顯子存在c.2867CA(p.S956X)無義突變,以上三個突變未見報(bào)道,均為新突變。在相應(yīng)表型正常的家庭成員及100名無親緣關(guān)系的正常個體中均未檢測出上述三個突變。結(jié)論:ADAR1基因移碼突變c.2638delG(p.Asp880ThrfsX15)、錯義突變c.3109AG(p.S1037G)和無義突變c.2867CA(p.S956X)可能分別是DSH家系1、家系2及散發(fā)病例發(fā)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.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R758.5

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