Clinical Features of Huntington's Disease
Clinical Features of Huntington's Disease
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DOI：
10.1007/978-3-319-71779-1_1
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Tabrizi, Sarah J.
中科院分区：
文献类型：
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作者：
Ghosh, Rhia;Tabrizi, Sarah J.
亨廷顿病(HD)是发达国家最常见的单基因神经退行性疾病和最常见的遗传性痴呆。由于常染色体显性遗传，典型的中年发病，以及15-20年来无情的进行性运动、认知和精神症状，它对患者及其家人的影响是毁灭性的。致病基因突变是编码Huntingtin蛋白的基因中一个扩大的CAG三核苷酸重复，导致该蛋白N-末端的聚谷氨酰胺延长。自从20多年前发现该基因以来，HD研究取得了很大进展，尽管目前还没有可以改变疾病的治疗方法，但有一些令人兴奋的潜在治疗进展正在酝酿之中。在这一章中，我们讨论了HD的流行病学、遗传学和发病机制，以及HD的临床表现和治疗，目前主要集中在对症治疗上。并对HD基因检测的原理进行了说明。还讨论了治疗学研究的最新进展，包括基因沉默和靶向小分子方法，以及寻找有助于验证这些潜在的新治疗方法的HD生物标志物。
Huntington's disease (HD) is the most common monogenic neurodegenerative disease and the commonest genetic dementia in the developed world. With autosomal dominant inheritance, typically mid-life onset, and unrelenting progressive motor, cognitive and psychiatric symptoms over 15-20 years, its impact on patients and their families is devastating. The causative genetic mutation is an expanded CAG trinucleotide repeat in the gene encoding the Huntingtin protein, which leads to a prolonged polyglutamine stretch at the N-terminus of the protein. Since the discovery of the gene over 20 years ago much progress has been made in HD research, and although there are currently no disease-modifying treatments available, there are a number of exciting potential therapeutic developments in the pipeline. In this chapter we discuss the epidemiology, genetics and pathogenesis of HD as well as the clinical presentation and management of HD, which is currently focused on symptomatic treatment. The principles of genetic testing for HD are also explained. Recent developments in therapeutics research, including gene silencing and targeted small molecule approaches are also discussed, as well as the search for HD biomarkers that will assist the validation of these potentially new treatments.