Garfinkel Amanda C, Seidman Jonathan G, Seidman Christine E
Department of Genetics, Harvard Medical School, New Research Building Room 256, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Department of Genetics, Brigham and Women's Hospital, Harvard Medical School, New Research Building Room 256, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA.
Heart Fail Clin. 2018 Apr;14(2):139-146. doi: 10.1016/j.hfc.2017.12.004.
Sarcomere cardiomyopathies are genetic diseases that perturb contractile function and lead to hypertrophic or dilated myocardial remodeling. Identification of preclinical mutation carriers has yielded insights into the earliest biomechanical defects that link pathogenic variants to cardiac dysfunction. Understanding this early molecular pathophysiology can illuminate modifiable pathways to reduce the emergence of overt cardiomyopathy and curb adverse outcomes. Here, the authors review current understandings of how human hypertrophic cardiomyopathy- and hypertrophic dilated cardiomyopathy-linked mutations disrupt the normal structure and function of the sarcomere.
肌节性心肌病是一种遗传性疾病，会扰乱收缩功能并导致肥厚性或扩张性心肌重塑。对临床前突变携带者的识别，已使人们深入了解了将致病变异与心脏功能障碍联系起来的最早生物力学缺陷。了解这种早期分子病理生理学，有助于阐明可改变的途径，以减少明显心肌病的出现并遏制不良后果。在此，作者综述了目前对于与人类肥厚性心肌病和肥厚性扩张型心肌病相关的突变如何破坏肌节正常结构和功能的理解。
