This study states that Hypertrophic cardiomyopathy (HCM) represents one of the most common inherited cardiac conditions. It is genetically and clinically heterogeneous and is most commonly caused by variants in sarcomere-encoding genes, including MYH7, which represents the second most common cause of familial HCM.1 Missense variants in MYH7 are believed to cause HCM through gain-of-function actions: Variants produce an abnormal activated protein that incorporates into the sarcomere as a poison peptide.2 Haploinsufficiency in MYH7 is not a recognized disease mechanism for HCM, and heterozygous variants that introduce premature termination codons (PTCs; ie, nonsense, frameshift, and splice variants) have not previously been demonstrated to be associated with this disease. Here, we report the frameshift variant c.5769delG in MYH7 that is associated with HCM in a large series of unrelated Egyptian patients with HCM assessed at the Aswan Heart Center. All patients gave written informed consent, and the study was reviewed and approved by the institutional research ethics committee Research Ethics Committee code.
Detailed study of a large family showed the cosegregation, and no other rare protein-altering variants were found in other established HCM genes.4 The proband carrying the frameshift variant presented with the disease at 29 years of age, and all affected family members carried the variant.
Reference link- https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.048295
