Hypertrophic cardiomyopathy (HCM) is caused by myocardial hypertrophy, often due to mutations in cardiac sarcomere protein genes such as beta-myosin heavy chain (MYH7) and myosin-binding protein C (MY Show more
Hypertrophic cardiomyopathy (HCM) is caused by myocardial hypertrophy, often due to mutations in cardiac sarcomere protein genes such as beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). However, a significant proportion of HCM cases lack identified genetic mutations, and genotype-phenotype correlations remain unclear. Concurrently, potential associations between HCM and human leukocyte antigen (HLA) types, as well as connective tissue diseases, have been proposed. In this single-center study, we aimed to investigate the genetic and HLA profiles of patients with obstructive hypertrophic cardiomyopathy (HOCM) and connective tissue diseases, particularly focusing on the prevalence of genetic variants and HLA types. We conducted a detailed analysis of five patients with HOCM and connective tissue diseases and sarcoidosis, identifying rare variants in causative genes for HCM in two cases and observing specific HLA types that were relatively common. Notably, 15% of all HOCM cases presented with connective tissue diseases, mainly rheumatoid arthritis. These findings underscore the complexity of HCM etiology and suggest potential implications for both diagnostic strategies and therapeutic approaches in patients with concomitant inflammatory conditions. Show less
Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patien Show more
Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patients with HCM develop a dilated phase of hypertrophic cardiomyopathy (D-HCM) and have poor prognosis; however, its pathogenesis is unclear and few pathological models exist. This study established disease-specific human induced pluripotent stem cells (iPSCs) from a patient with D-HCM harboring a mutation in MYBPC3 (c.1377delC), a common causative gene of HCM, and investigated the associated pathophysiological mechanisms using disease-specific iPSC-derived cardiomyocytes (iPSC-CMs). We confirmed the expression of pluripotent markers and the ability to differentiate into three germ layers in D-HCM patient-derived iPSCs (D-HCM iPSCs). D-HCM iPSC-CMs exhibited disrupted myocardial sarcomere structures and an increased number of damaged mitochondria. Ca Show less