Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy

Mori, Augusto Akira; Castro, Lara Reinel de; Bortolin, Raul Hernandes; Bastos, Gisele Medeiros; Oliveira, Victor Fernandes de; Ferreira, Gláucio Monteiro; Hirata, Thiago Dominguez Crespo; Fajardo, Cristina Moreno; Sampaio, Marcelo Ferraz; Moreira, Dalmo Antônio Ribeiro; Pachón-Mateos, José Carlos; Correia, Edileide de Barros; Sousa, Amanda Guerra de Moraes Rego; Brión, Marı́a; Carracedo, Ángel; Hirata, Rosário Dominguez Crespo; Hirata, Mário Hiroyuki

doi:10.1016/j.fsigen.2021.102478

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…This is because genes can affect the expression of nearby or distant genes, and some of these variants have recently been associated with the development of cardiac pathologies [111]. Moreover, as said, structural anomalies tend to be progressive and may cause arrhythmias in the young even before the complete development of the phenotype [112][113][114]. Proper sampling and storage of the blood and/or of the tissues (liver, spleen and/or heart) for the genetic testing is crucial for optimizing the results of the procedure.…”

Section: Molecular Autopsymentioning

confidence: 99%

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Grassi

Campuzano

Coll

et al. 2021

IJMS

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Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.

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Section: Molecular Autopsymentioning

confidence: 99%

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Grassi

Campuzano

Coll

et al. 2021

IJMS

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“…MYH7 contributes to movement and contraction, especially in cardiac cells, and plays a vital role in the sarcomere structure and heartbeat. Any mutation in MHY7 can influence contractile properties and form-function relationship (32,38) by affecting its binding to actin, MYBPC3, and TNNT2. The normal MYH7 can also regulate ATP consumption and protein-protein interaction, and as a result, the binding regions of this protein and accompanying proteins are crucial to the function of myosin (39).…”

Section: Discussionmentioning

confidence: 99%

A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction

Hesaraki

Bora

Pahlavan

et al. 2022

Front. Cardiovasc. Med.

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Cardiomyopathies are a group of common heart disorders that affect numerous people worldwide. Left ventricular non-compaction (LVNC) is a structural disorder of the ventricular wall, categorized as a type of cardiomyopathy that mostly caused by genetic disorders. Genetic variations are underlying causes of developmental deformation of the heart wall and the resultant contractile insufficiency. Here, we investigated a family with several affected members exhibiting LVNC phenotype. By whole-exome sequencing (WES) of three affected members, we identified a novel heterozygous missense variant (c.1963C>A:p.Leu655Met) in the gene encoding myosin heavy chain 7 (MYH7). This gene is evolutionary conserved among different organisms. We identified MYH7 as a highly enriched myosin, compared to other types of myosin heavy chains, in skeletal and cardiac muscles. Furthermore, MYH7 was among a few classes of MYH in mouse heart that highly expresses from early embryonic to adult stages. In silico predictions showed an altered actin-myosin binding, resulting in weaker binding energy that can cause LVNC. Moreover, CRISPR/Cas9 mediated MYH7 knockout in zebrafish caused impaired cardiovascular development. Altogether, these findings provide the first evidence for involvement of p.Leu655Met missense variant in the incidence of LVNC, most probably through actin-myosin binding defects during ventricular wall morphogenesis.

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“…Furthermore, a meta-analysis of 7675 HCM patients showed that HCM patients with MYH7 mutations had an earlier age of onset, resulting in a more severe phenotype [ 98 ]. MYH7 p.Val320Met contributes to the increased risk of sudden cardiac death of hypertrophic cardiomyopathy [ 99 ]. It is worth noting that small molecule drugs, such as mavacamten and aficamten, targeting myosin have been employed in clinical trials for treatment of HCM [ 97 , 100 , 101 ].…”

Section: Abps In Cardiac Hypertrophymentioning

confidence: 99%

Actin-Binding Proteins in Cardiac Hypertrophy

Pan

Wang

Liu

et al. 2022

Cells

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The heart reacts to a large number of pathological stimuli through cardiac hypertrophy, which finally can lead to heart failure. However, the molecular mechanisms of cardiac hypertrophy remain elusive. Actin participates in the formation of highly differentiated myofibrils under the regulation of actin-binding proteins (ABPs), which provides a structural basis for the contractile function and morphological change in cardiomyocytes. Previous studies have shown that the functional abnormality of ABPs can contribute to cardiac hypertrophy. Here, we review the function of various actin-binding proteins associated with the development of cardiac hypertrophy, which provides more references for the prevention and treatment of cardiomyopathy.

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Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy

Cited by 9 publications

References 44 publications

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

A Novel Missense Variant in Actin Binding Domain of MYH7 Is Associated With Left Ventricular Noncompaction

Actin-Binding Proteins in Cardiac Hypertrophy

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