Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.; Department of Advanced Cardiac Therapeutics, Fukushima Medical University, Fukushima, Japan.
Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.; Department of Advanced Cardiac Therapeutics, Fukushima Medical University, Fukushima, Japan..
Clin Chim Acta. 2019 Aug;495:123-128. doi: 10.1016/j.cca.2019.04.005. Epub 2019 Apr 5.
Titin, encoded by the gene TTN, is the largest human protein, and plays central roles in sarcomeric structures and functions in skeletal and cardiac muscles. Mutations of TTN are causally related to specific types of muscular dystrophies and cardiomyopathies. A developed methodology of next generation sequencing has recently led to the identification of novel TTN mutations in such diseases. The clinical significance of titin is now emerging as a target for genetic strategies. Titin-related muscular dystrophies include tibial muscular dystrophy, limb-girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, hereditary myopathy with early respiratory failure, central core myopathy, centronuclear myopathies, and Salih myopathy. Truncation mutations of TTN have been identified as the most frequent genetic cause of dilated cardiomyopathy. In this review article, we highlight the role of titin and impact of TTN mutations in the pathogenesis of muscular dystrophies and cardiomyopathies. Recently, a novel sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of the urinary titin N-terminal fragments (U-TN) has been established. We discuss the clinical significance of U-TN in the diagnosis of muscular dystrophies and differential diagnosis of cardiomyopathies, as well as risk stratification in dilated cardiomyopathy.
肌联蛋白由 TTN 基因编码，是人体内最大的蛋白，在骨骼肌和心肌的肌节结构和功能中发挥核心作用。TTN 基因突变与特定类型的肌肉疾病和心肌病有因果关系。新一代测序技术的发展方法最近导致了这些疾病中新型 TTN 突变的鉴定。肌联蛋白的临床意义现在作为遗传策略的靶点正在显现。与肌联蛋白相关的肌肉疾病包括胫骨肌营养不良症、肢带型肌肉营养不良症、Emery-Dreifuss 肌肉营养不良症、遗传性伴早发呼吸衰竭的肌病、中央核肌病、中心核肌病和 Salih 肌病。TTN 的截断突变已被确定为扩张型心肌病最常见的遗传原因。在这篇综述文章中，我们强调了肌联蛋白的作用以及 TTN 突变对肌肉疾病和心肌病发病机制的影响。最近，建立了一种新型的敏感夹心酶联免疫吸附试验（ELISA）用于检测尿肌联蛋白 N 端片段（U-TN）。我们讨论了 U-TN 在肌肉疾病诊断和心肌病鉴别诊断中的临床意义，以及扩张型心肌病的风险分层。
