PDF(Pubmed)
Abstract：
Myocardial bridging (MB) is a congenital coronary artery anomaly and an important cause of angina. The genetic basis of MB is currently unknown. This study used a whole-exome sequencing technique and analyzed genotypic differences. Eight coronary angiography-confirmed cases of severe MB and eight age- and sex-matched control patients were investigated. In total, 139 rare variants that are potentially pathogenic for severe MB were identified in 132 genes. Genes with multiple rare variants or co-predicted by ClinVar and CADD/REVEL for severe MB were collected, from which heart-specific genes were selected under the guidance of tissue expression levels. Functional annotation indicated significant genetic associations with abnormal skeletal muscle mass, cardiomyopathies, and transmembrane ion channels. Candidate genes were reviewed regarding the functions and locations of each individual gene product. Among the gene candidates for severe MB, rare variants in DMD, SGCA, and TTN were determined to be the most crucial. The results suggest that altered anchoring proteins on the cell membrane and intracellular sarcomere unit of cardiomyocytes play a role in the development of the missed trajectory of coronary vessels. Additional studies are required to support the diagnostic application of cardiac sarcoglycan and dystroglycan complexes in patients with severe MB.
摘要：
心肌桥（MB）是先天性冠状动脉异常，是心绞痛的重要病因。MB的遗传基础目前尚不清楚。这项研究使用了全外显子组测序技术并分析了基因型差异。调查了8例经冠状动脉造影证实的重度MB病例和8例年龄和性别匹配的对照患者。总的来说,在132个基因中鉴定出139种可能导致严重MB的罕见变异。收集具有多种罕见变异或由ClinVar和CADD/REVEL共同预测的严重MB的基因，在组织表达水平的指导下从中选择心脏特异性基因。功能注释表明与异常骨骼肌质量显著遗传关联，心肌病,和跨膜离子通道。关于每个单独基因产物的功能和位置审查了候选基因。在严重MB的候选基因中，DMD中罕见的变种,SGCA,TTN被认为是最关键的。结果表明，心肌细胞细胞膜和细胞内肌节单元上锚定蛋白的改变在冠状血管错过轨迹的发展中起作用。需要更多的研究来支持心脏肌聚糖和肌聚糖复合物在重度MB患者中的诊断应用。
