重庆地区脊髓小脑性共济失调的分子研究及临床分析

发布时间：2018-06-26 04:42

本文选题：脊髓小脑性共济失调 + 基因　；参考：《重庆医科大学》2014年硕士论文

【摘要】：目的：通过调查重庆地区临床诊断为脊髓小脑性共济失调的家系及散发患者，了解该地区脊髓小脑性共济失调的基因分型及临床表现。方法：1.召集2011年1月至2013年12月于重庆医科大学附属第一医院、附属第二医院神经内科就诊，并诊断为SCAs的10个家系中19例患者及28例血亲，同时召集9例散发患者。绘制SCAs家系患者的家系图。对所有受试者进行详细的神经系统查体。部分患者行脑部磁共振检查。2.取外周静脉血提取基因组，使用聚合酶链反应法（Polymerase Chain Reaction，PCR）对所有受试者SCA1、SCA2、SCA3、SCA6、SCA7、SCA12、SCA17及RPLA基因进行扩增及DNA直接测序。3.结合临床及影像资料对重庆地区SCA3患者进行分析。结果：1.本研究中10个SCAs家系中有8个SCA3家系，另2个家系及9例散发患者未能明确分型，未发现SCA1、SCA2、SCA6、SCA7、SCA12、SCA17及DRPLA亚型。2.正常对照组ATXN3基因CAG重复次数为8-39次，15例SCA3患者ATXN3基因CAG重复次数为58-71次，7例症状前患者ATXN3基因CAG重复次数为56-71次。子代CAG重复次数较亲代有增加趋势，在父系遗传中更突出。3. SCA3患者临床表现复杂，主要表现为共济失调及构音障碍，平均发病年龄为49.6±5.6岁，存在明显的遗传早现现象，且在父系遗传中尤为突出。4. SCA3患者大脑萎缩不明显，，主要表现幕下脑萎缩，并以小脑蚓部尤为明显。脑干萎缩程度与病程正相关，病程越长，萎缩越明显。结论：重庆地区的SCAs主要为SCA3型，与我国其他地区的报道一致。主要表现为共济失调及构音障碍，具有典型的临床异质性及遗传早现，且遗传早现在父系遗传中尤为突出，脑部影像学表现为幕下脑萎缩。临床表现及影像学表现为诊断本病提供重要依据，基因检测是目前确诊本病的唯一方法。
[Abstract]:Objective: to investigate the genotyping and clinical manifestations of spinal cerebellar ataxia in Chongqing area by investigating the families and sporadic patients who were clinically diagnosed as spinal cerebellar ataxia. Method 1: 1. From January 2011 to December 2013, 19 patients and 28 blood relatives of 10 families of the first affiliated Hospital of Chongqing Medical University and the second affiliated Hospital of Chongqing Medical University were invited to visit the Department of Neurology, and 9 sporadic patients were called together at the same time. Draw up the pedigree map of the patients in the family of scas. All subjects were given a detailed neurological examination. Some patients underwent brain magnetic resonance imaging. 2. 2. The genomic DNA was extracted from peripheral venous blood. The SCA1, SCA2, SCA3, SCA7, SCA12, SCA17 and RPLA genes were amplified by polymerase chain reaction (PCR) and the DNA was directly sequenced. 3. Combined with clinical and imaging data, SCA 3 patients in Chongqing area were analyzed. The result is 1: 1. In this study, there were 8 SCA3 families in 10 SCAs families, 2 families and 9 sporadic patients were not clearly classified, and no SCA1, SCA2, SCA6, SCA7, SCA12, SCA17 and DRPLA subtype. 2 were found in SCA1, SCA2, SCA6, SCA7, SCA12, SCA17 and DRPLA subtypes. The number of CAG repeats of ATXN3 gene in 15 patients with SCA3 was 58-71 times and the number of CAG repeats of ATXN3 gene was 56-71 times in 7 presymptomatic patients. The number of repeat of CAG in progeny was higher than that of parents, and it was more prominent in patrilineal inheritance. The clinical manifestations of SCA3 patients were complex, mainly ataxia and dysarthria. The average onset age was 49.6 卤5.6 years old. There was an obvious genetic preexisting phenomenon in SCA3 patients, especially in patrilineal inheritance. The cerebral atrophy was not obvious in SCA 3 patients, especially in cerebellar vermis. The degree of brain stem atrophy was positively correlated with the course of disease, and the longer the course, the more obvious the atrophy. Conclusion: the main type of scas in Chongqing is SCA 3, which is consistent with the reports in other regions of China. The main manifestations are ataxia and dysarthria, with typical clinical heterogeneity and early genetic appearance, especially in patriarchal heredity. The brain imaging manifestations are subtentorial brain atrophy. Clinical manifestations and imaging findings provide important basis for the diagnosis of this disease, gene detection is the only way to diagnose the disease.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R744.7

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