UCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK.
Adv Exp Med Biol. 2018;1049:1-28. doi: 10.1007/978-3-319-71779-1_1.
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.
亨廷顿病（HD）是最常见的单基因神经退行性疾病，也是发达国家最常见的遗传性痴呆症。具有常染色体显性遗传、典型的中年发病、15-20 年内持续进行性运动、认知和精神症状，对患者及其家庭的影响是毁灭性的。致病基因突变是编码亨廷顿蛋白的基因中 CAG 三核苷酸重复的扩展，导致蛋白 N 端的多谷氨酰胺延伸。自 20 多年前发现该基因以来，HD 研究取得了很大进展，尽管目前尚无疾病修饰治疗方法，但有许多令人兴奋的潜在治疗方法正在开发中。本章讨论了 HD 的流行病学、遗传学和发病机制以及 HD 的临床表现和管理，目前主要集中在对症治疗上。还解释了 HD 基因检测的原则。还讨论了治疗研究的最新进展，包括基因沉默和靶向小分子方法，以及寻找 HD 生物标志物，以协助验证这些潜在的新治疗方法。
