Abstract
BACKGROUND: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most frequent cardiomyopathies that cause acute heart failure and sudden cardiac death. Previous genetic reports have shown that pathogenic variants of genes encoding Z-disc components such as telethonin protein (TCAP) are the primary cause of DCM and HCM. METHODS: This study was the first investigation on the TCAP gene among the Iranian cardiomyopathies population wherein the TCAP gene was analyzed in 40 unrelated patients (17 females and 23 males) who were clinically diagnosed with HCM and DCM. In addition, we conducted a thorough review of all published articles and the databases that were the first to report novel pathogenic or likely pathogenic variants the in TCAP gene. RESULTS: In the cohort of this study, we identified only one intronic variant c.111-42G > A in one of the HCM patients that were predicted as polymorphism by in-silico analysis. Moreover, a total of 44 variants were reported for the TCAP gene in the literature where a majority of mutations were found to be missense. Pathogenic mutations in TCAP may cause diseases including limb-girdle muscular dystrophy 2G (LGMD-2G), DCM, HCM, intestinal pseudo-obstruction, and telethonin deficiency. However, a large number of affected patients were clinically diagnosed with limb-girdle 2G compared to other presenting phenotypes. DISCUSSION: These findings suggest that the TCAP gene pathogenic mutations might not be a common cause of cardiomyopathies among Iranian patients. These gene disease-causing mutations may cause various manifestations, but it has a high prevalence among LGMD-2G, HCM, and DCM patients.