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Abstract：
The Z-disc acts as a protein-rich structure to tether thin filament in the contractile units, the sarcomeres, of striated muscle cells. Proteins found in the Z-disc are integral for maintaining the architecture of the sarcomere. They also enable it to function as a (bio-mechanical) signalling hub. Numerous proteins interact in the Z-disc to facilitate force transduction and intracellular signalling in both cardiac and skeletal muscle. This review will focus on six key Z-disc proteins: α-actinin 2, filamin C, myopalladin, myotilin, telethonin and Z-disc alternatively spliced PDZ-motif (ZASP), which have all been linked to myopathies and cardiomyopathies. We will summarise pathogenic variants identified in the six genes coding for these proteins and look at their involvement in myopathy and cardiomyopathy. Listing the Minor Allele Frequency (MAF) of these variants in the Genome Aggregation Database (GnomAD) version 3.1 will help to critically re-evaluate pathogenicity based on variant frequency in normal population cohorts.
摘要：
Z盘作为一种富含蛋白质的结构，在收缩单元中束缚细丝，肉瘤，横纹肌细胞。在Z-盘中发现的蛋白质对于维持肌节的结构是不可或缺的。他们还使它作为一个（生物机械）信号枢纽。许多蛋白质在Z-椎间盘中相互作用以促进心肌和骨骼肌中的力转导和细胞内信号传导。本文将重点介绍六种关键的Z-椎间盘蛋白:α-肌动蛋白2、丝素C、Myopalladin,肌动蛋白,远花素和Z盘交替剪接的PDZ基序（ZASP），这些都与肌病和心肌病有关。我们将总结在编码这些蛋白质的六个基因中鉴定的致病变异，并研究它们在肌病和心肌病中的参与。在基因组聚集数据库（GnomAD）3.1版中列出这些变体的次要等位基因频率（MAF）将有助于根据正常人群队列中的变体频率重新评估致病性。
