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Research Article: Sarcomeric versus Non-Sarcomeric HCM

Date Published: 2023-06-02

Abstract:
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disorder and is characterized by left ventricular hypertrophy (LVH), which is unexplained by abnormal loading conditions. HCM is inherited as an autosomal dominant trait and, in about 40% of patients, the causal mutation is identified in genes encoding sarcomere proteins. According to the results of genetic screening, HCM patients are currently categorized in two main sub-populations: sarcomeric-positive (Sarc+) patients, in whom the causal mutation is identified in a sarcomeric gene; and sarcomeric-negative (Sarc?) patients, in whom a causal mutation has not been identified. In rare cases, Sarc? HCM cases may be caused by pathogenic variants in non-sarcomeric genes. The aim of this review is to describe the differences in the phenotypic expression and clinical outcomes of Sarc+ and Sarc? HCM and to briefly discuss the current knowledge about HCM caused by rare non-sarcomeric mutations.

Introduction:
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, with a prevalence of 1 in 500 individuals; it is characterized by asymmetric left ventricular (LV) hypertrophy, which is not explained by an overload caused by other cardiac or systemic diseases [1,2,3]. HCM has been the focus of intense clinical and basic science investigation for decades, since the discovery of the first mutation in the Myosin Heavy Chain-7 (MYH7) gene, encoding ?-cardiac myosin heavy chain (?-MHC), in 1989 [4]. Research…

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