PDF(Pubmed)
Abstract：
Pediatric cardiomyopathies are mostly attributed to variants in sarcomere-related genes. Unfortunately, the genetic architecture of pediatric cardiomyopathies has never been previously studied in Jordan. We sought to uncover the genetic landscape of 14 patients from nine families with several subtypes of pediatric cardiomyopathies in Jordan using Exome sequencing (ES). Our investigation identified pathogenic and likely pathogenic variants in seven out of nine families (77.8%), clustering in sarcomere-related genes. Surprisingly, phenocopies of sarcomere-related hypertrophic cardiomyopathies were evident in probands with glycogen storage disorder and mitochondrial-related disease. Our study underscored the significance of streamlining ES or expanding cardiomyopathy-related gene panels to identify plausible phenocopies of sarcomere-related cardiomyopathies. Our findings also pointed out the need for genetic testing in patients with cardiomyopathy and their at-risk family members. This can potentially lead to better management strategies, enabling early interventions, and ultimately enhancing their prognosis. Finally, our findings provide an initial contribution to the currently absent knowledge about the molecular underpinnings of cardiomyopathies in Jordan.
摘要：
小儿心肌病主要归因于肌节相关基因的变异。不幸的是,约旦以前从未研究过小儿心肌病的遗传结构.我们试图通过Exome测序（ES）揭示来自约旦9个患有几种亚型小儿心肌病的家庭的14名患者的遗传前景。我们的调查确定了九个家庭中的七个（77.8％）的致病性和可能的致病性变异，肌节相关基因的聚类。令人惊讶的是,在糖原贮积障碍和线粒体相关疾病的先证者中，肌节相关肥厚型心肌病的表型明显。我们的研究强调了简化ES或扩展心肌病相关基因面板以鉴定肌节相关心肌病的合理表型的重要性。我们的发现还指出了对心肌病患者及其高危家庭成员进行基因检测的必要性。这可能会导致更好的管理策略，能够进行早期干预，并最终提高他们的预后。最后,我们的发现为约旦目前缺乏的关于心肌病分子基础的知识提供了初步贡献.
