International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 42-53 http://medscipublisher.com/index.php/ijmms 48 Additionally, a study on Spanish patients identified MYH7 mutations (Met822Val and Arg453Cys) in individuals with severe forms of HCM, illustrating the phenotypic heterogeneity among carriers (García-Castro et al., 2003). 7.2 Gene function studies Research on SCN5Amutations has provided insights into their role in arrhythmias. A study on a Japanese family identified a novel SCN5A gain-of-function mutation (M1875T) associated with familial atrial fibrillation. Functional assays demonstrated that this mutation led to increased atrial excitability, a novel mechanism distinct from long-QT syndrome type 3 (Makiyama et al., 2008). Another study reported a family with a SCN5A c.611C>A variant linked to Dilated Cardiomyopathy (DCM) and multifocal ectopic Purkinje-related premature contractions (MEPPC). The combination of SCN5A and PRKAG2 mutations in this family resulted in severe cardiac phenotypes, including glycogen accumulation in the myocardium (Huang et al, 2022). Additionally, promoter variants in SCN5A were found to be associated with the severity of arrhythmia phenotypes in a family with a heterozygous loss-of-function mutation, highlighting the complexity of genetic interactions (Park et al., 2012). 7.3 Validation of novel therapeutic strategies While specific studies on gene editing for TPM1 mutations were not provided, the concept of using gene editing to correct genetic mutations in familial hypertensive heart disease is supported by the broader context of genetic research. For example, the identification of specific mutations in MYH7 and SCN5A genes and their associated phenotypes underscores the potential for targeted genetic therapies. The functional assays and clinical evaluations of these mutations provide a foundation for developing gene editing strategies aimed at correcting pathogenic variants and restoring normal cardiac function (Makiyama et al., 2008; Zhang et al., 2018; Huang et al, 2022). Zhang et al. (2018) conducted a detailed evaluation of left atrial lesions using CMR, including left atrial wall thickening and significant late gadolinium enhancement. These features may suggest inflammatory or fibrotic conditions such as atrial myocarditis or idiopathic left atrial fibrosis (Figure 3). These imaging findings provide important evidence for assessing and diagnosing related conditions, such as atrial fibrillation, heart failure, or cryptogenic stroke. Figure 3 Cardiac Magnetic Resonance Images (Adopted from Zhang et al., 2018) Image caption: (A) Steady-state free precession cine showing normal left ventricular chamber size and wall thickness and an enlarged left atrium with thickened walls. (B) T2-weighted dark blood image with fat suppression (triple inversion recovery) revealing atrial wall thickening that is not consistent with lipomatous hypertrophy. (C) Late gadolinium enhancement image showing transmural enhancement of the left atrial wall and absence of enhancement in the left ventricular myocardium. (D) The white line indicates the approximate short-axis location for images E and F. (E) Short-axis image with T2-weighted triple inversion recovery showing nearly circumferential thickening of the left atrium (LA). (F) Multiple inversion recovery image (cine inversion recovery) with inversion time optimized to demonstrate left atrial enhancement (Adopted from Zhang et al., 2018)
RkJQdWJsaXNoZXIy MjQ4ODYzNA==