Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Department of Nursing, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Medicina (Kaunas). 2023 Jun 16;59(6):1158. doi: 10.3390/medicina59061158.
: The maturation of cardiomyocytes is a rapidly evolving area of research within the field of cardiovascular medicine. Understanding the molecular mechanisms underlying cardiomyocyte maturation is essential to advancing our knowledge of the underlying causes of cardiovascular disease. Impaired maturation can lead to the development of cardiomyopathy, particularly dilated cardiomyopathy (DCM). Recent studies have confirmed the involvement of the and genes in the maturation process, facilitating the functional maturation of the sarcomere and calcium handling. Defective sarcomere and electrophysiological maturation have been linked to severe forms of cardiomyopathy. This report presents a rare case of DCM with myocardial non-compaction, probably resulting from allelic collapse of both the and genes. : The proband in this case was a four-year-old male child who presented with a recurrent and aggressive reduction in activity tolerance, decreased ingestion volume, and profuse sweating. Electrocardiography revealed significant ST-T segment depression (II, III, aVF V3-V6 ST segment depression >0.05 mV with inverted T-waves). Echocardiography showed an enlarged left ventricle and marked myocardial non-compaction. Cardiac magnetic resonance imaging revealed increased left ventricular trabeculae, an enlarged left ventricle, and a reduced ejection fraction. Whole exome sequencing revealed a restricted genomic depletion in the 1q43 region (chr1:236,686,454-237,833,988/Hg38), encompassing the coding genes , , and . The identified variant resulted in heterozygous variations in these three genes, with the g.236,686,454-236,764,631_del and g.237,402,134-237,833,988_del variants being the dominant contributors to the induction of cardiomyopathy. The patient was finally diagnosed with DCM and left ventricular myocardial non-compaction. : This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the and genes. This case provides the first human validation of the critical role of cardiomyocyte maturation in maintaining cardiac function and stability and confirms the key findings of previous experimental research conducted by our group. This report emphasizes the connection between genes involved in regulating the maturation of cardiomyocytes and the development of cardiomyopathy.
心肌细胞的成熟是心血管医学领域中一个快速发展的研究领域。了解心肌细胞成熟的分子机制对于深入了解心血管疾病的潜在原因至关重要。成熟受损可导致心肌病的发生，特别是扩张型心肌病（DCM）。最近的研究证实了 和 基因在成熟过程中的参与，促进了肌节和钙处理的功能成熟。肌节和电生理成熟的缺陷与严重形式的心肌病有关。本报告介绍了一例罕见的 DCM 合并心肌致密化不全，可能是由于 和 基因的等位基因崩溃所致。
本病例的先证者为 4 岁男性患儿，反复出现活动耐力进行性下降、摄入减少和大量出汗。心电图显示明显的 ST-T 段压低（II、III、aVF、V3-V6 导联 ST 段压低>0.05 mV，伴倒置 T 波）。超声心动图显示左心室扩大和明显的心肌致密化不全。心脏磁共振成像显示左心室小梁增多、左心室扩大和射血分数降低。全外显子组测序显示 1q43 区域（chr1：236,686,454-237,833,988/Hg38）存在受限的基因组缺失，包括编码基因 、 和 。鉴定的变异导致这三个基因的杂合变异，其中 g.236,686,454-236,764,631_del 和 g.237,402,134-237,833,988_del 变异是诱导心肌病的主要原因。患者最终诊断为 DCM 和左心室心肌致密化不全。
本研究报告了一例罕见的由 和 基因的等位基因崩溃引起的 DCM 合并心肌致密化不全病例。该病例首次为人提供了心肌细胞成熟在维持心脏功能和稳定性方面的关键作用的验证，并证实了我们小组之前进行的实验研究的关键发现。本报告强调了调节心肌细胞成熟的基因与心肌病发生之间的联系。
