Darwish Rania K, Haghighi Alireza, Seliem Zeinab S, El-Saiedi Sonia A, Radwan Nora H, El-Gayar Dina F, Elfeel Nesrine S, Abouelhoda Mohamed, Mehaney Dina A
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Next-Generation sequencing Laboratory, Cairo University Children Hospital, Cairo, Egypt.
Cardiol Young. 2020 Dec;30(12):1910-1916. doi: 10.1017/S1047951120003157. Epub 2020 Oct 5.
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.
小儿心肌病是一种进行性且通常致命的疾病，是儿童心力衰竭最常见的病因。尽管其后果严重，但其遗传病因仍未得到充分表征。本研究旨在通过靶向二代测序揭示一组埃及儿童特发性原发性肥厚型心肌病的遗传背景。该研究纳入了24例患者（15例男性和9例女性），他们前往开罗大学儿童医院心肌病门诊就诊，中位年龄为2.75岁（0.5 - 14岁）。62.5%的患者存在近亲结婚情况。20.8%的患者有肥厚型心肌病家族史。在8例患者中检测到10个罕见变异；其中MBPC3和MYH7中有2个致病变异（8.3%），MYBPC3、TTN、VCL、MYL2、CSRP3和RBM20中有8个意义未明的变异。在此，我们报告埃及第一项全国性研究，该研究使用二代测序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。当前的初步研究表明，埃及小儿肥厚型心肌病可能具有特定的遗传背景，尤其是近亲结婚负担较重。在常规诊断服务中纳入基因检测对于更好地理解疾病的病理生理学、妥善管理患者以及检测风险很重要。全基因组检测（全外显子组/基因组测序）除了能够识别新的遗传病因外，可能比靶向测序方法更适合检测原发性肥厚型心肌病患者。
