Schneider Susanne A, Bhatia Kailash P
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.
Handb Clin Neurol. 2011;100:101-12. doi: 10.1016/B978-0-444-52014-2.00005-7.
Huntington's disease (HD) is caused by a triplet repeat expansion in the IT15 gene on chromosome 4 encoding huntingtin. Gene mutations are found in about 99% of cases, with symptoms and signs suggestive of HD. This implies the existence of other causes of this syndrome, and, in recent years, several other distinct genetic disorders have been identified that can present with a clinical picture indistinguishable from HD, termed HD-like (HDL) syndromes. So far, four genes associated with HDL syndromes have been identified, including the prion protein gene (HDL1), the junctophilin 3 gene (HDL2) and, the gene encoding the TATA box-binding protein (HDL4). In addition, a single family with a recessively inherited HD phenocopy, the exact genetic basis of which is currently unknown (HDL3), has been described. These disorders, however, account for only a small proportion of HDL cases, and the list of HDL genes and conditions is set to grow. In this article, we review the currently identified HD phenocopy disorders and discuss clinical clues to facilitate further investigations. We will concentrate on the four so-called HDL syndromes mentioned above. Other genetic choreatic syndromes such as dentatorubral-pallidoluysian atrophy, neuroferritinopathy, pantothenate kinase-associated neurodegeneration, and chorea-acanthocytosis are also briefly discussed.
亨廷顿舞蹈病（HD）由4号染色体上编码亨廷顿蛋白的IT15基因中的三联体重复扩增引起。约99%的病例存在基因突变，伴有提示HD的症状和体征。这意味着该综合征存在其他病因，近年来，已鉴定出其他几种不同的遗传疾病，它们可表现出与HD难以区分的临床症状，称为类亨廷顿舞蹈病（HDL）综合征。到目前为止，已鉴定出与HDL综合征相关的四个基因，包括朊蛋白基因（HDL1）、连接膜蛋白3基因（HDL2）以及编码TATA盒结合蛋白的基因（HDL4）。此外，还描述了一个具有隐性遗传HD表型模拟的家系，其确切遗传基础目前尚不清楚（HDL3）。然而，这些疾病仅占HDL病例的一小部分，HDL基因和病症的清单还会增加。在本文中，我们回顾了目前已鉴定出的HD表型模拟疾病，并讨论有助于进一步研究的临床线索。我们将重点关注上述四种所谓的HDL综合征。还简要讨论了其他遗传性舞蹈病综合征，如齿状核红核苍白球路易体萎缩症、神经铁蛋白病、泛酸激酶相关神经变性和舞蹈病性棘红细胞增多症。
