背景: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提高我们对心血管疾病根本原因的认识至关重要。成熟受损会导致心肌病的发展,特别是扩张型心肌病(DCM)。最近的研究证实ACTN2和RYR2基因参与成熟过程,促进肌节的功能成熟和钙处理。肌节缺陷和电生理成熟与严重的心肌病有关。本报告介绍了一例罕见的DCM伴心肌致密化,可能是由于ACTN2和RYR2基因的等位基因崩溃所致。病例介绍:在这种情况下,先证者是一个四岁的男孩,他表现出活动耐受性的反复和积极的降低,摄入量减少,大量出汗。心电图显示明显的ST-T段压低(II,III,aVFV3-V6ST段压低>0.05mV,带有倒T波)。超声心动图显示左心室增大,心肌致密化明显。心脏磁共振成像显示左心室小梁增加,左心室增大,射血分数降低.全外显子组测序显示1q43区域的基因组耗竭(chr1:236,686,454-237,833,988/Hg38),包括编码基因ACTN2、MTR、RYR2鉴定的变异导致这三个基因的杂合变异,ACTN2g.236,686,454-236,764,631_del和RYR2g.237,402,134-237,833,988_del变体是诱发心肌病的主要贡献者。患者最终诊断为DCM和左心室心肌致密化不全。结论:本研究报告了一例罕见的DCM,由ACTN2和RYR2基因的等位基因塌陷引起的心肌致密化不全。该病例首次验证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,并证实了我们小组先前进行的实验研究的关键发现。该报告强调了参与调节心肌细胞成熟的基因与心肌病发展之间的联系。
Background: 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
ACTN2 and RYR2 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
ACTN2 and RYR2 genes. Case Presentation: 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
ACTN2, MTR, and RYR2. The identified variant resulted in heterozygous variations in these three genes, with the
ACTN2 g.236,686,454-236,764,631_del and RYR2 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. Conclusions: This study reports a rare case of DCM with myocardial non-compaction caused by the allelic collapse of the
ACTN2 and RYR2 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.