First application of next-generation sequencing in patients with hypertrophic cardiomyopathy in Morocco and report of a novel frameshift mutation of MYBPC3 gene: Case report

Background: Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by an unexplained left ventricular hypertrophy (LVH), usually asymmetrical and involving the interventricular septum. HCM is a relatively frequent disorder, affecting one of 500 individuals from the general population. Some patients may not have any symptoms during their whole life, whereas in other cases, HCM may lead to severe symptoms such as syncope or dyspnea, sudden death, or congestive heart failure. It remains the most prevalent cause of in-explained sudden death in athletes during exercise. HCM is a familial disease in at least 50% of cases, with mainly an autosomal dominant mode of inheritance with variable expression and incomplete penetrance. It may be also inherited in autosomal recessive pattern or X-linked manner. HCM are caused by mutations in nearly 22 different genes, > 17 genes are involved in autosomal dominant HCM. The most frequently mutations fall within myosin heavy chain 7 (MYH7) and myosin binding protein C (MYBPC3), both accounting for up to 50% of HCM cases. Case presentation: The present study reports the molecular results of a series of six unrelated Moroccan patients with HCM using for the first time in Morocco a next generation sequencing (NGS) customized multigene panel to investigate the two major HCM genes MYH7 and MYBPC3. Genetic testing lead to the identification of a novel MYBPC mutation (c.1049delA; p.Lys350fs) and three others previously described variants at heterozygous state. Conclusion: Molecular diagnosis by NGS customized multigenes panel allowed us to set up a fast and firstline upon request cost-efficient strategy in order to screen various genes and diseases including HCM. This approach is well suited to general medical genetics laboratories dealing with almost all types of rare genetic diseases with limited funds for a molecular testing more cost-effective.