發(fā)布時(shí)間：2018-02-07 14:05

  本文關(guān)鍵詞： 脊髓小腦性共濟(jì)失調(diào)2型 帕金森病 ATXN2基因 三核苷酸重復(fù)　出處：《中南大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景：脊髓小腦性共濟(jì)失調(diào)2型(SCA2)是一種常染色體顯性遺傳脊髓小腦性共濟(jì)失調(diào)亞型(AD-SCA),其致病是位于12q23-24染色體上的ATXN2基因1號(hào)外顯子的CAG三核苷酸異常重復(fù)擴(kuò)增所致。SCA2占SCA患病總?cè)藬?shù)的3%-47%,在意大利、英國(guó)、印度等國(guó)家常見,主要臨床表現(xiàn)為運(yùn)動(dòng)協(xié)調(diào)功能障礙,部分患者可合并錐體外系表現(xiàn)。 目的：了解SCA2在中國(guó)大陸SCA患病人群中的頻率分布；研究ATXN2基因CAG三核苷酸重復(fù)與中國(guó)大陸家族性帕金森病(PD)的關(guān)聯(lián)；進(jìn)一步了解SCA2及PD-SCA2患者臨床特點(diǎn)及ATXN2基因CAG三核苷酸重復(fù)次數(shù)、重復(fù)序列打斷情況對(duì)SCA2、PD-SCA2患者臨床表型的影響。 方法：對(duì)713個(gè)常染色體顯性遺傳SCA家系、444名散發(fā)SCA患者及75個(gè)常染色體顯性遺傳PD家系進(jìn)行臨床總結(jié),應(yīng)用PCR擴(kuò)增、變性聚丙烯酰胺凝膠電泳、毛細(xì)管凝膠電泳及T載體連接克隆測(cè)序等方法進(jìn)行ATXN2基因CAG三核苷酸重復(fù)次數(shù)及序列測(cè)定,并運(yùn)用Mann-Whitney U檢驗(yàn)、線性回歸分析法等對(duì)結(jié)果進(jìn)行統(tǒng)計(jì)分析。 結(jié)果：在713個(gè)AD-SCA家系中檢測(cè)出59個(gè)SCA2家系(8.28%),在444名S-SCA患者中檢測(cè)出10名SCA2患者(2.25%)；在75個(gè)常染色體顯性遺傳PD家系中檢測(cè)出6個(gè)PD-SCA2家系(8%)；SCA2患者臨床表現(xiàn)多樣,錐體外系癥狀較常見,PD-SCA2患者起病年齡大于SCA2患者組,大多不伴有共濟(jì)失調(diào)表現(xiàn)且抗帕金森病藥物有效；PD-SCA2患者的ATXN2基因CAG三核苷酸重復(fù)次數(shù)明顯偏小,和SCA2患者存在顯著差異； SCA2患者中ATXN2基因CAG三核苷酸重復(fù)次數(shù)與患者發(fā)病年齡呈負(fù)相關(guān),貢獻(xiàn)度為58.9%,PD-SCA2患者中則無(wú)此規(guī)律；SCA2患者組ATXN2基因CAG三核苷酸重復(fù)序列以無(wú)CAA打斷最常見(85.71%),PD-SCA2患者組及正常對(duì)照組則以1到2次CAA打斷最常見,分別占76.92%和93%,三組重復(fù)序列CAA打斷模式兩兩間均存在顯著差異； SCA2患者組的3’端CAG三核苷酸重復(fù)序列結(jié)尾時(shí)被1次CCG打斷最常見(38.46%),PD-SCA2患者組及正常對(duì)照組則以無(wú)CCG打斷最常見,分別占92.31%和100%。SCA2患者組與正常對(duì)照組、SCA2患者組與PD-SCA2患者組的3’端CCG打斷模式有顯著差異,但PD-SCA2患者組與正常對(duì)照組間無(wú)顯著差異。 結(jié)論： 1、SCA2是中國(guó)漢族SCA家系中除SCA3外最常見亞型,在常染色體顯性遺傳家系中占8.28%,在散發(fā)患者中占2.25%； 2、ATXN2基因異常重復(fù)擴(kuò)增可導(dǎo)致帕金森樣表型,ATXN2基因可能是中國(guó)漢族家族性PD的致病基因； 3.ATXN2基因CAG三核苷酸重復(fù)次數(shù)、重復(fù)序列CAA打斷模式及3’端CCG打斷模式可能與SCA2及PD-SCA2患者表型有關(guān)。
[Abstract]:Background: Spinal cerebellar ataxia type 2 (SCA2) is an autosomal dominant spinal cerebellar ataxia subtype AD-SCA2, which causes abnormal CAG trinucleotide amplification of exon 1 of ATXN2 gene on chromosome 12q23-24. SCA2 accounted for 3%-47% of the total number of patients with SCA, in Italy, In Britain, India and other countries, the main clinical manifestation is motor coordination dysfunction, some patients can be combined with extrapyramidal system. Objective: to investigate the frequency distribution of SCA2 in the population with SCA in mainland China, and to study the association between CAG trinucleotide repeat of ATXN2 gene and familial Parkinson's disease (PD) in mainland China. To investigate the clinical characteristics of SCA2 and PD-SCA2 patients and the influence of CAG trinucleotide repeats of ATXN2 gene on the clinical phenotypes of patients with SCA2P PD-SCA2. Methods: 444 autosomal dominant SCA pedigrees and 75 autosomal dominant PD families were analyzed by PCR amplification and denatured polyacrylamide gel electrophoresis. Capillary gel electrophoresis (CE) and T-vector ligation cloning and sequencing were used to determine the CAG trinucleotide repeat number and sequence of ATXN2 gene. Mann-Whitney U test and linear regression analysis were used to analyze the results. Results: 59 SCA2 families were detected in 713 AD-SCA families, 10 out of 444 S-SCA patients with SCA2, and 6 PD-SCA2 families in 75 autosomal dominant PD families. The onset age of PD-SCA2 patients with common extrapyramidal symptoms was higher than that of SCA2 patients, and most of them had no ataxia and the ATXN2 gene CAG trinucleotide repeats of PD-SCA2 patients with effective antiParkinson disease drugs were significantly smaller than those of SCA2 patients. The number of ATXN2 gene CAG trinucleotide repeats in SCA2 patients was negatively correlated with the age of onset. The ATXN2 gene CAG trinucleotide repeat sequence in the SCA2 group was the most common in the PD-SCA2 patient group and the normal control group with one or two CAA interruptions with no CAA interrupting the CAG trinucleotide repeat sequence in the PD-SCA2 patients and in the normal control group, and the results showed that the CAG trinucleotide repeat sequence of the ATXN2 gene was most common in the patients with PD-SCA2 and in the normal control group. 76.92% and 93%, respectively. There were significant differences between the two groups of repeated sequence CAA interruption patterns. The 3'end CAG trinucleotide repeat at the end of the 3'end of the SCA2 group was most frequently interrupted by once CCG. The most common interruption was no CCG in the PD-SCA2 patient group and the normal control group. The 3'end CCG interruption pattern in SCA2 group and normal control group was significantly different from that in PD-SCA2 group, but there was no significant difference between PD-SCA2 group and normal control group. Conclusion:. 1SCA2 is the most common subtype of SCA in Chinese Han nationality, except SCA3, which accounts for 8.28% in autosomal dominant families and 2.25% in sporadic patients. 2abnormal repeat amplification of ATXN2 gene may lead to Parkinson's like phenotypic gene ATXN2 gene may be the pathogenic gene of Chinese Han nationality familial PD. 3. The number of CAG trinucleotide repeats in ATXN2 gene, the CAA interruption pattern of repeat sequence and the 3'terminal CCG interruption pattern may be related to the phenotypes of SCA2 and PD-SCA2 patients.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R744.7

【共引文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前2條

1 陸海鵬;中國(guó)東部人群肌萎縮側(cè)索硬化ATXN2基因CAG重復(fù)的檢測(cè)與分析[D];福建醫(yī)科大學(xué);2013年

2 魏飛飛;Ataxin-3的亞細(xì)胞定位及其對(duì)細(xì)胞器形態(tài)的影響[D];中南大學(xué);2013年

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本文編號(hào)：1494552