Abstract：
Mutations in genes encoding proteins associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex within the nuclear envelope cause different diseases with varying phenotypes including skeletal muscle, cardiac, metabolic, or nervous system pathologies. There is some understanding of the structure of LINC complex-associated proteins and how they interact, but it is unclear how mutations in genes encoding them can cause the same disease, and different diseases with different phenotypes. Here, published mutations in LINC complex-associated proteins were systematically reviewed and analyzed to ascertain whether patterns exist between the genetic sequence variants and clinical phenotypes. This revealed LMNA is the only LINC complex-associated gene in which mutations commonly cause distinct conditions, and there are no clear genotype-phenotype correlations. Clusters of LMNA variants causing striated muscle disease are located in exons 1 and 6, and metabolic disease-associated LMNA variants are frequently found in the tail of lamin A/C. Additionally, exon 6 of the emerin gene, EMD, may be a mutation \"hot-spot\", and diseases related to SYNE1, encoding nesprin-1, are most often caused by nonsense type mutations. These results provide insight into the diverse roles of LINC-complex proteins in human disease and provide direction for future gene-targeted therapy development.
摘要：
编码与核膜内的核骨架和细胞骨架（LINC）复合物的接头相关的蛋白质的基因突变导致具有不同表型的不同疾病，包括骨骼肌，心脏,新陈代谢，或神经系统病变。人们对LINC复合物相关蛋白的结构以及它们如何相互作用有一些了解，但目前还不清楚编码它们的基因突变如何导致同样的疾病，和具有不同表型的不同疾病。这里,我们对已发表的LINC复合物相关蛋白的突变进行了系统回顾和分析,以确定基因序列变异和临床表型之间是否存在模式.这表明LMNA是唯一的LINC复合物相关基因，其中突变通常会导致不同的条件，并且没有明确的基因型-表型相关性。导致横纹肌疾病的LMNA变体簇位于外显子1和6中，与代谢疾病相关的LMNA变体经常在层粘连蛋白A/C的尾巴中发现。此外,emerin基因的外显子6,EMD,可能是一个突变\“热点\”，和与SYNE1相关的疾病，编码nesprin-1，最常由无义型突变引起。这些结果为了解LINC复合物蛋白在人类疾病中的不同作用提供了见解，并为未来的基因靶向治疗发展提供了方向。
