本文選題：遺傳性對(duì)稱性色素異常癥 + ADAR1基因��； 參考：《濟(jì)南大學(xué)》2012年碩士論文

【摘要】：研究背景遺傳性對(duì)稱性色素異常癥（Dyschromatosis symmetric hereditaria，DSH,MIM127400），又名Dohi對(duì)稱性肢端色素沉著癥,為常染色體顯性遺傳的良性皮膚病，主要臨床特點(diǎn)是肢體末端由色素沉著和色素減退形成的網(wǎng)狀斑，皮損主要分布于手背及腳背，部分患者在面部可有雀斑樣損壞。本病常于嬰兒期或者兒童期發(fā)病，青春期停止發(fā)展，并持續(xù)終生。2003年，張學(xué)軍等采用全基因組掃描的方法對(duì)2個(gè)家系進(jìn)行分析，第一次將本病致病基因定位在1q11-1q21區(qū)間約116cM的區(qū)域隨后，日本學(xué)者M(jìn)iyamura等對(duì)四個(gè)DSH家系進(jìn)行全基因組掃描，，將本病的致病基因精細(xì)定位于1q21.3約500kb的區(qū)域內(nèi)，并在這四個(gè)家系中均發(fā)現(xiàn)雙鏈RNA特異性腺苷脫氨酶基因（DSRAD/ADAR1基因）的雜合突變，本突變?cè)谡?duì)照中未發(fā)現(xiàn)，證明這些堿基的改變是突變不而是多態(tài)，因此首次確定了DSRAD/ADAR1基因?yàn)楸静〉闹虏』�。DSRAD/ADAR1基因是一種雙鏈RNA特異性腺昔脫氨酶,主要生物學(xué)功能包括RNA編輯和誘導(dǎo)蛋白質(zhì)在核內(nèi)的翻譯。該基因所編碼的雙鏈RNA特異性的腺苷酸脫氨酶選擇性的作用于前體信使RNA,將特殊位點(diǎn)上的腺嘌呤核苷(A)經(jīng)過(guò)脫氨基作用轉(zhuǎn)換成次黃嘌呤核苷(I),次黃嘌呤核苷在堿基配對(duì)中相當(dāng)于鳥嘌呤(G)和胞嘧啶(C)的配對(duì),導(dǎo)致雙鏈RNA結(jié)構(gòu)的不穩(wěn)定及mRNA降解,并由此產(chǎn)生特定的生理學(xué)效應(yīng)。迄今為止，國(guó)內(nèi)外共發(fā)現(xiàn)了121個(gè)有關(guān)DSH的ADAR1基因突變位點(diǎn)，遺憾的是，沒有發(fā)現(xiàn)熱點(diǎn)突變。本研究收集4個(gè)DSH散發(fā)病例，通過(guò)DNA直接測(cè)序?qū)ζ銩DAR1基因進(jìn)行了檢測(cè)。 目的對(duì)4個(gè)散發(fā)的遺傳性對(duì)稱性色素異常癥病例的ADAR1基因進(jìn)行突變檢測(cè)。 方法收集整理4個(gè)散發(fā)的遺傳性對(duì)稱性色素異常癥患者的臨床資料。獲得知情同意后，抽取患者血樣，提取患者外周血脫氧核糖核苷酸（DNA），采用聚合酶鏈反應(yīng)擴(kuò)增患者和100名無(wú)親緣關(guān)系的正常對(duì)照個(gè)體ADAR1基因的全部外顯子序列，然后對(duì)P C R擴(kuò)增產(chǎn)物直接測(cè)序并進(jìn)行序列分析，檢測(cè)該基因突變。 結(jié)果通過(guò)對(duì)4個(gè)散發(fā)的遺傳性對(duì)稱性色素異常癥患者ADAR1基因的突變檢測(cè)，檢測(cè)到1個(gè)曾被報(bào)道過(guò)的錯(cuò)義突變3463C T (p.R1155W)和兩個(gè)未曾報(bào)道的突變：1605delT (p.F535fs)框移突變和c.1630C T (p.R544x)無(wú)義突變。而在100例正常對(duì)照中均為發(fā)現(xiàn)上述突變。 結(jié)論本研究通過(guò)PCR及DNA測(cè)序，發(fā)現(xiàn)了2個(gè)新的突變，包括一個(gè)框移突變和一個(gè)無(wú)義突變。進(jìn)一步豐富了ADAR1基因數(shù)據(jù)庫(kù)，為研究遺傳性對(duì)稱性色素異常癥的發(fā)病機(jī)理及其基因型和表型之間的關(guān)系提供了新的數(shù)據(jù)。同時(shí)為將來(lái)這四個(gè)病例進(jìn)行產(chǎn)前診斷或孕前診斷、提供遺傳學(xué)咨詢、阻斷本病在家系中的遺傳奠定了重要的基礎(chǔ)。
[Abstract]:Background Dyschromatosis symmetric dyschromatosis symmetric hereditariade MIM127400, also known as Dohi symmetries, is an autosomal dominant benign skin disease characterized by pigmentation and hypochromatic reticular plaques at the extremities. Skin lesions are mainly distributed on the back of the hand and the back of the foot, and some patients may have freckle damage on the face. The disease often occurs in infancy or childhood, stops developing during puberty, and lasts for life. In 2003, Zhang Xuejun and others used a genome-wide scanning method to analyze two families. For the first time, the disease-causing gene was located in the region of the 1q11-1q21 region about 116cM. Then, Japanese scholar Miyamura et al scanned the whole genome of four DSH families, and mapped the disease-causing gene in the region of 1q21.3 about 500kb. Heterozygous mutations of the double stranded RNA specific adenosine deaminase gene (DSRAD / ADAR1 gene) were found in all four families, and this mutation was not found in normal controls, indicating that the changes in these bases were not mutations but polymorphic. Therefore, it is the first time that the DSRAD/ADAR1 gene. DSRAD / ADAR1 gene is a double stranded RNA specific adenodeaminase. Its main biological functions include RNA editing and inducing protein translation in the nucleus. The double-stranded adenylate deaminase encoded by the gene selectively acts on the precursor messenger RNAs, converting adenine nucleoside (A) at specific sites into Hypoxanthine nucleoside (I), which is in the base of the nucleoside Hypoxanthine (Hypoxanthine). A pair corresponding to guanine and cytosine C) in the base pairing. It leads to instability of double stranded RNA structure and degradation of mRNA, resulting in specific physiological effects. Up to now, 121 ADAR1 mutation sites related to DSH have been found at home and abroad, but unfortunately, no hot spot mutations have been found. In this study, four sporadic DSH cases were collected and their ADAR1 genes were detected by DNA sequencing. Objective to detect the mutation of ADAR1 gene in 4 sporadic cases of hereditary symmetrical dystrophy. Methods the clinical data of 4 sporadic patients with dystrophy of hereditary symmetry were collected. After obtaining informed consent, all exon sequences of ADAR1 gene were amplified by polymerase chain reaction (PCR) from patients' blood samples, DNA of deoxyribonucleotides (DNA) from peripheral blood of patients and 100 unrelated normal individuals. The PCR products were sequenced and sequenced to detect the mutation. Results by detecting the ADAR1 gene mutations in 4 sporadic patients with dystrophy, a previously reported missense mutation of 3463C T / p. R1155W) and two unreported mutations: 1 / 1605delT / p. F535fs) and c. 1630C / T / p. R544x) were detected. These mutations were found in 100 normal controls. Conclusion in this study, two new mutations were identified by PCR and DNA sequencing, including one box shift mutation and one nonsense mutation. It further enriches the ADAR1 gene database and provides new data for the study of the pathogenesis and the relationship between genotypes and phenotypes of hereditary symmetric pigmented disorders. At the same time, it lays an important foundation for prenatal diagnosis or pre-pregnancy diagnosis in the future, providing genetic counseling and blocking the inheritance of the disease in the home line.
【學(xué)位授予單位】：濟(jì)南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R758.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 何平平,張學(xué)軍,林國(guó)書,崔勇,肖尚喜,李誠(chéng)讓,王再興,高敏,宋映雪,楊森;遺傳性對(duì)稱性色素異常癥:臨床和遺傳特點(diǎn)分析[J];安徽醫(yī)科大學(xué)學(xué)報(bào);2001年06期

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