Paediatric Neurology Research Group, Hospital Vall d'Hebrón, Universitat Autònoma de Barcelona, Vall d'Hebrón Research Institute, Barcelona, Spain.
Universitat Autònoma de Barcelona, Barcelona, Spain.
Mol Neurobiol. 2021 Aug;58(8):3938-3952. doi: 10.1007/s12035-021-02391-0. Epub 2021 Apr 22.
Myoclonus-dystonia (MD) is a rare childhood-onset movement disorder, with an estimated prevalence of about 2 per 1,000,.000 in Europe, characterized by myoclonic jerks in combination with focal or segmental dystonia. Pathogenic variants in the gene encoding ε-sarcoglycan (SGCE), a maternally imprinted gene, are the most frequent genetic cause of MD. To date, the exact role of ε-sarcoglycan and the pathogenic mechanisms that lead to MD are still unknown. However, there are more than 40 reported isoforms of human ε-sarcoglycan, pointing to a complex biology of this protein. Additionally, some of these are brain-specific isoforms, which may suggest an important role within the central nervous system. In the present review, we aim to provide an overview of the current state of knowledge of ε-sarcoglycan. We will focus on the genetic landscape of SGCE and the presence and plausible role of ε-sarcoglycan in the brain. Finally, we discuss the importance of the brain-specific isoforms and hypothesize that SGCE may play essential roles in normal synaptic functioning and their alteration will be strongly related to MD.
肌阵挛-肌张力障碍（MD）是一种罕见的儿童期发病的运动障碍疾病，在欧洲的患病率约为每 100 万人中有 2 例。其特征是肌阵挛性抽搐与局灶性或节段性肌张力障碍相结合。编码 ε- 肌聚糖（SGCE）的基因中的致病变异体，是 MD 的最常见遗传原因。迄今为止，ε- 肌聚糖的确切作用和导致 MD 的致病机制仍不清楚。然而，人类 ε- 肌聚糖有超过 40 种报道的异构体，这表明该蛋白具有复杂的生物学特性。此外，其中一些是大脑特异性异构体，这可能表明其在中枢神经系统中具有重要作用。在本综述中，我们旨在概述 ε- 肌聚糖的现有知识状态。我们将重点介绍 SGCE 的遗传景观以及 ε- 肌聚糖在大脑中的存在和可能的作用。最后，我们讨论了大脑特异性异构体的重要性，并假设 SGCE 可能在正常突触功能中发挥重要作用，其改变将与 MD 密切相关。
