这篇全面的MDSGene综述致力于7个基因-TOR1A,THAP1,GNAL,ANO3,PRKRA,KMT2B,和HPCA-可能导致孤立性肌张力障碍的突变。它遵循MDSGene的标准化数据提取协议,总共筛选了约1200条引文。收集并分析了具有254种不同突变的1200名患者的表型和基因型数据。发病年龄存在差异,发病部位,以及所有7个基因中突变携带者的症状分布。虽然TOR1A的载体,THAP1PRKRA,KMT2B,或HPCA突变主要表现为儿童和青少年发病,GNAL和ANO3突变的患者通常在成年期出现首发症状.GNAL和KMT2B突变携带者通常有1个主要的发病位点,也就是说,颈部(GNAL)或下肢(KMT2B),而DYT-TOR1A的发病部位,DYT-THAP1,DYT-ANO3,DYT-PRKRA,DYT-HPCA范围更广。然而,在大多数DYT-THAP1和DYT-ANO3患者中,肌张力障碍首先表现在身体的上半部分(上肢,脖子,和颅面/喉),而在DYT-TOR1A中发作,经常在四肢观察到DYT-PRKRA和DYT-HPCA,包括上部和下部。对于ANO3,典型的是分段/多焦点分布,而TOR1A,PRKRA,KMT2B,HPCA突变携带者通常发展为广泛性肌张力障碍。THAP1突变携带者伴有病灶,节段性/多灶性,或几乎相等比例的广泛性肌张力障碍。GNAL突变携带者很少表现出普遍性。这篇综述全面概述了遗传性孤立性肌张力障碍的最新知识。数据也可在在线数据库中获得(http://www。mdsgen.org),它还提供了描述性汇总统计数据。©2021作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
This comprehensive MDSGene
review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed MDSGene\'s standardized data extraction protocol and screened a total of ~1200 citations. Phenotypic and genotypic data on ~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This
review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.