Wang Xi, Zabell Allyson, Koh Wonshill, Tang W H Wilson
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland, OH, USA.
Children's Hospital of Pittsburgh, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Curr Treat Options Cardiovasc Med. 2017 Mar;19(3):21. doi: 10.1007/s11936-017-0520-z.
Dilated cardiomyopathy (DCM) is the third leading cause of heart failure in the USA. A major gene associated with DCM with cardiac conduction system disease is lamin A/C (LMNA) gene. Lamins are type V filaments that serve a variety of roles, including nuclear structure support, DNA repair, cell signaling pathway mediation, and chromatin organization. In 1999, LMNA was found responsible for Emery-Dreifuss muscular dystrophy (EDMD) and, since then, has been found in association with a wide spectrum of diseases termed laminopathies, including LMNA cardiomyopathy. Patients with LMNA mutations have a poor prognosis and a higher risk for sudden cardiac death, along with other cardiac effects like dysrhythmias, development of congestive heart failure, and potential need of a pacemaker or ICD. As of now, there is no specific treatment for laminopathies, including LMNA cardiomyopathy, because the mechanism of LMNA mutations in humans is still unclear. This review discusses LMNA mutations and how they relate to DCM, the necessity for further investigation to better understand LMNA mutations, and potential treatment options ranging from clinical and therapeutic to cellular and molecular techniques.
扩张型心肌病（DCM）是美国心力衰竭的第三大主要病因。与伴有心脏传导系统疾病的DCM相关的一个主要基因是核纤层蛋白A/C（LMNA）基因。核纤层蛋白是V型细丝，发挥多种作用，包括支持核结构、DNA修复、介导细胞信号通路以及染色质组织。1999年，发现LMNA与埃默里 - 德赖富斯肌营养不良症（EDMD）有关，从那时起，已发现它与多种被称为核纤层蛋白病的疾病相关，包括LMNA心肌病。携带LMNA突变的患者预后较差，心脏性猝死风险较高，还会出现其他心脏问题，如心律失常、充血性心力衰竭的发展以及可能需要起搏器或植入式心脏除颤器（ICD）。截至目前，对于包括LMNA心肌病在内的核纤层蛋白病尚无特异性治疗方法，因为人类中LMNA突变的机制仍不清楚。本综述讨论了LMNA突变及其与DCM的关系、进一步研究以更好理解LMNA突变的必要性，以及从临床治疗到细胞和分子技术等潜在的治疗选择。
