钙调蛋白在心脏病中的作用:基因型和表型的启示

IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Peter J Schwartz, Lia Crotti, Mette Nyegaard, Michael Toft Overgaard
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引用次数: 0

摘要

钙调素是一种对所有主要心脏离子通道的调节都极为重要的蛋白质,是最典型的细胞钙传感器,在保持心电稳定性方面发挥着关键作用。在 3 条不同的染色体上有 3 个基因编码相同的蛋白,而且这些基因的结构极其稳定,这凸显了钙调素蛋白的独特重要性。事实上,所有 3 个钙调素(CALM)基因都是人类基因组中最受限制的基因之一,也就是说,观察到的变异远低于偶然的预期。不足为奇的是,CALM 变异的耐受性很差,并伴有显著的临床表型,其中最重要的是那些与危及生命的心律失常风险增加相关的变异。在此,我们回顾了有关钙调蛋白的现有知识、其特定的生理、结构和功能特征及其对心血管疾病的重要性。鉴于我们在这一知识的发展过程中扮演的角色,我们还分享了我们对目前尚未解答的问题的一些看法,包括对受影响患者进行临床管理的合理方法。具体来说,我们介绍了从我们十年前建立的国际钙调蛋白病登记处获得的一些最关键的信息。我们发现,要取得进一步的进展,就必须通过国际上对该登记处的贡献来收集深层表型信息,这是扩大我们对钙调素病的了解的最佳途径,目的是获得必要的信息来指导临床治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role of Calmodulin in Cardiac Disease: Insights on Genotype and Phenotype.

Calmodulin, a protein critically important for the regulation of all major cardiac ion channels, is the quintessential cellular calcium sensor and plays a key role in preserving cardiac electrical stability. Its unique importance is highlighted by the presence of 3 genes in 3 different chromosomes encoding for the same protein and by their extreme conservation. Indeed, all 3 calmodulin (CALM) genes are among the most constrained genes in the human genome, that is, the observed variants are much less than expected by chance. Not surprisingly, CALM variants are poorly tolerated and accompany significant clinical phenotypes, of which the most important are those associated with increased risk for life-threatening arrhythmias. Here, we review the current knowledge about calmodulin, its specific physiological, structural, and functional characteristics, and its importance for cardiovascular disease. Given our role in the development of this knowledge, we also share some of our views about currently unanswered questions, including the rational approaches to the clinical management of the affected patients. Specifically, we present some of the most critical information emerging from the International Calmodulinopathy Registry, which we established 10 years ago. Further progress clearly requires deep phenotypic information on as many carriers as possible through international contributions to the registry, in order to expand our knowledge about Calmodulinopathies and guide clinical management.

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来源期刊
Circulation: Genomic and Precision Medicine
Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
9.20
自引率
5.40%
发文量
144
期刊介绍: Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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