小儿心肌病是一种进行性且通常致命的疾病,是儿童心力衰竭的最常见原因。尽管结果很严重,他们的遗传病因仍然缺乏表征。目前的研究旨在揭示特发性原发性肥厚型心肌病的遗传背景在埃及儿童队列中使用靶向下一代测序。该研究包括24名患者(男性15名,女性9名),他们在开罗大学儿童医院的心肌病诊所就诊,中位年龄为2.75(0.5-14)岁。62.5%的患者血缘关系呈阳性。20.8%的患者存在肥厚型心肌病的家族史。在8例患者中检测到10例罕见变异;MBPC3和MYH7中有2例致病性变异(8.3%),MYBPC3,TTN,VCL,MYL2、CSRP3和RBM20。这里,我们报道了在埃及进行的第一项全国性研究,该研究使用下一代测序技术分析了一组特发性小儿肥厚型心肌病患者的肌节和非肌节变异.目前的初步研究表明,埃及的小儿肥厚型心肌病可能具有特定的遗传背景,尤其是血缘关系的高负担。在常规诊断服务中包括基因检测对于更好地了解疾病的病理生理学非常重要,适当的病人管理,和风险检测。全基因组测试(全外显子组/基因组测序)可能比靶向测序方法更好地测试原发性肥厚型心肌病患者,除了其识别新的遗传原因的能力。
Paediatric cardiomyopathy is a progressive and often lethal disorder and the most common cause of heart failure in children. Despite their severe outcomes, their genetic etiology is still poorly characterised. The current
study aimed at uncovering the genetic background of idiopathic primary hypertrophic cardiomyopathy in a cohort of Egyptian children using targeted next-generation sequencing. The
study included 24 patients (15 males and 9 females) presented to the cardiomyopathy clinic of Cairo University Children\'s Hospital with a median age of 2.75 (0.5-14) years. Consanguinity was positive in 62.5% of patients. A family history of hypertrophic cardiomyopathy was present in 20.8% of patients. Ten rare variants were detected in eight patients; two pathogenic variants (8.3%) in MBPC3 and MYH7, and eight variants of uncertain significance in MYBPC3, TTN, VCL, MYL2, CSRP3, and RBM20.Here, we report on the first national
study in Egypt that analysed sarcomeric and non-sarcomeric variants in a cohort of idiopathic paediatric hypertrophic cardiomyopathy patients using next-generation sequencing. The current pilot
study suggests that paediatric hypertrophic cardiomyopathy in Egypt might have a particular genetic background, especially with the high burden of consanguinity. Including the genetic testing in the routine diagnostic service is important for a better understanding of the pathophysiology of the disease, proper patient management, and at-risk detection. Genome-wide tests (whole exome/genome sequencing) might be better than the targeted sequencing approach to test primary hypertrophic cardiomyopathy patients in addition to its ability for the identification of novel genetic causes.