Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetic disorder characterised by the early development of muscle contractures, progressive muscle weakness, and heart abnormalities. The latter may result in serious complications, or in severe cases, sudden death. Currently, there are very few effective treatment options available for EDMD and so there is a high clinical need for new therapies. Various genetic mutations have been identified in the development and causation of EDMD, each encoding proteins that are components of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, which spans the nuclear envelope and serves to connect the nuclear lamina to the cytoskeleton. Within this review, we examine how mutations in the genes encoding these proteins, including lamins A/C, emerin, nesprins 1/2, FHL1, and SUN1/2 lead to muscle cell differentiation and development pathway defects. Further work to identify conserved molecular pathways downstream of these defective proteins may reveal potential targets for therapy design.

中文翻译：

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Emery-Dreifuss肌营养不良症的肌细胞分化和发育途径缺陷

Emery-Dreifuss 肌营养不良症 (EDMD) 是一种罕见的遗传性疾病，其特征是肌肉挛缩、进行性肌无力和心脏异常的早期发展。后者可能会导致严重的并发症，严重的会导致猝死。目前，可用于 EDMD 的有效治疗方案很少，因此临床对新疗法的需求很高。在 EDMD 的发展和病因中已经确定了各种基因突变，每种基因突变都编码作为核骨架和细胞骨架连接器 (LINC) 复合物的组成部分的蛋白质，该复合物跨越核膜并将核层与细胞骨架连接起来。在这篇综述中，我们研究了编码这些蛋白质的基因的突变，包括 lamins A/C、emerin、nesprins 1/2、FHL1、和SUN1/2导致肌细胞分化和发育途径缺陷。进一步确定这些缺陷蛋白下游保守分子途径的工作可能会揭示治疗设计的潜在目标。