Phenotypic diversity of cardiomyopathy caused by an mybpc3 frameshift mutation in a Korean family: A case report

Restrictive cardiomyopathy (RCM) is one of the rarest cardiac disorders, with a very poor prognosis, and heart transplantation is the only long-term treatment of choice. We reported that a Korean family presented different cardiomyopathies, such as idiopathic RCM and hypertrophic cardiomyopathy (HCM), caused by the same MYBPC3 mutation in different individuals. A 74-year-old male was admitted for the evaluation of exertional dyspnea, palpitations, and pitting edema in both legs for several months. Transthoracic echocardiography (TTE) showed RCM with biatrial enlargement and pericardial effusion. Cardiac magnetic resonance (CMR) images revealed normal left ventricular chamber size, borderline diffuse left ventricular hypertrophy and very large atria. In contrast to the proband, CMR images showed asymmetric septal hypertrophy of the left ventricle, consistent with a diagnosis of HCM in the proband’s two daughters. Of the five heterozygous variants identified as candidate causes of inherited cardiomyopathy by whole exome sequencing in the proband, Sanger sequencing confirmed the presence of a heterozygous frameshift mutation (NM_000256.3:c.3313_3314insGG; p.Ala1105Glyfs*85) in MYBPC3 in the proband and his affected daughters, but not in his unaffected granddaughter. There is clinical and genetic overlap of HCM with restrictive physiology and RCM, especially when HCM is combined with severe myocardial fibrosis. Family screening with genetic testing and CMR imaging could be excellent tools for the evaluation of idiopathic RCM.