Molecular Diagnosis of Hypertrophic Cardiomyopathy (HCM): In the Heart of Cardiac Disease

Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease with the presence of left ventricular hypertrophy (LVH). The disease is characterized by high locus, allelic and phenotypic heterogeneity, even among members of the same family. The list of confirmed and potentially relevant genes implicating the disease is constantly increasing, with novel genes frequently reported. Heterozygous alterations in the five main sarcomeric genes (MYBPC3, MYH7, TNNT2, TNNI3, and MYL2) are estimated to account for more than half of confirmed cases. The genetic discoveries of recent years have shed more light on the molecular pathogenic mechanisms of HCM, contributing to substantial advances in the diagnosis of the disease. Genetic testing applying next-generation sequencing (NGS) technologies and early diagnosis prior to the clinical manifestation of the disease among family members demonstrate an important improvement in the field.

Keywords: genetic testing; hypertrophic cardiomyopathy (HCM); next generation sequencing.

Figure 1

Hypertrophic cardiomyopathy (HCM) is caused by transcriptomic defects in certain proteins of the sarcomere as a result of specific genomic alterations on thick and thin filaments and Z-disks. Abbreviations: cMyBP-C, cardiac myosin binding protein C; Tm, tropomyosin; TnT, troponin T; TnI, troponin I; TnC, troponin C; MHC, myosin heavy chain; MLC1-2, myosin light chain 1-2.