Genetic study of pediatric hypertrophic cardiomyopathy in Egypt

Abstract

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.

miR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients

“…Many different etiologic factors were described to cause myocardial damage in DCM [25]. According to cardiomyopathies-relevant Egyptian studies, positive consanguinity could be risk factors in the cardiomyopathies etiology, where Darwish et al [26] reported a first study to uncovering the genetic background of idiopathic primary hypertrophic cardiomyopathy in 24 Egyptian patients with 62.5% positive consanguinity; they pointed the high burden of consanguinity in Egyptian pediatric hypertrophic cardiomyopathy might associate with particular genetic background. Mehaney et al [27] pointed that 53% of the studies dilated cardiomyopathy patients showed positive consanguinity, and the authors suggested that high burden of consanguinity might lead to novel genes or variants underlie pediatric cardiomyopathy in Egyptian DCM patients.…”

Molecular analysis of dilated and left ventricular noncompaction cardiomyopathies in Egyptian children

“…Methods for clinical genetic workup and bioinformatic data analysis have been described previously. 17 Clinical workup included (a) documenting the family history and pedigree. If two or more closely related family members were affected, they were classified as familial 18 ; (b) documenting the medical history with the assessment of heart failure symptoms using ROSS/NYHA classification 19 ; (c) full physical and cardiac examination; and (d) radiological investigations including chest X-ray and two-dimensional echocardiography.…”

Mechanisms of RBM20 Cardiomyopathy: Insights From Model Systems

“…The original report by Brauch et al 19 identified 6 pathogenic variants in RBM20 all located within the RS domain, in what, based on our recent work, 30 we now know to be the core NLS. Since this initial study, many additional RBM20 variants have been reported both in and outside the RS domain in association with disease, 13,20,26,46,48,49,52,53,55,56,59–88 and the number continues to increase. Although variants have now been identified throughout the RBM20 protein, the windows c.1881–1920 (encoding the NLS in exon 9) and c.2721–2760 (encoding a portion of the glutamate-rich region in exon 11) represent the 2 currently accepted hotspots for DCM-associated variants (Figure 1B and 1C).…”