4.6 Review

Genotype-Phenotype Correlations in Human Diseases Caused by Mutations of LINC Complex-Associated Genes: A Systematic Review and Meta-Summary

期刊

CELLS
卷 11, 期 24, 页码 -

出版社

MDPI
DOI: 10.3390/cells11244065

关键词

LINC complex; nuclear envelope; laminopathies; lamin A; C; LMNA; SYNE1; EMD; nesprin; emerin

向作者/读者索取更多资源

Mutations in genes encoding proteins associated with the LINC complex can cause different diseases, but the relationship between genetic mutations and clinical phenotypes is still unclear. LMNA is the only gene where mutations commonly cause distinct conditions and there is no clear genotype-phenotype correlation. These findings provide insights into the role of LINC-complex proteins in human disease and guide future gene-targeted therapies.
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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据