Genetic variations of β-MYH7 in hypertrophic cardiomyopathy and dilated cardiomyopathy

Tanjore, Reena R.; Rangaraju, Advithi; Vadapalli, Shivani; Remersu, Sushant; Calambur, Narsimhan; Nallari, Pratibha

doi:10.4103/0971-6866.69348

Cited by 15 publications

(8 citation statements)

References 13 publications

(15 reference statements)

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“…The mechanisms underlying the onset of cardiomyopathy in, e.g. , RBM20 deficiency involve incorrect processing of several splicing targets at once, including important contractile and structural proteins, such as calcium/calmodulin-dependent protein kinase II delta (CaMKIId), ryanodine receptor, tropomyosin, troponin, and titin, thereby affecting the structural and functional properties of cardiomyocytes including calcium handling [20] , [21] , [22] .…”

Section: Introductionmentioning

confidence: 99%

SLM2 Is a Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy

Boeckel

Möbius-Winkler²,

Müller

et al. 2021

Genomics, Proteomics &Amp; Bioinformatics

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Alternative mRNA splicing is a fundamental process to increase the versatility of the genome. In humans, cardiac mRNA splicing is involved in the pathophysiology of heart failure. Mutations in the splicing factor RNA binding motif protein 20 (RBM20) cause severe forms of cardiomyopathy. To identify novel cardiomyopathy-associated splicing factors, RNA-seq and tissue-enrichment analyses were performed, which identified up-regulated expression of Sam68-Like mammalian protein 2 (SLM2) in the left ventricle of dilated cardiomyopathy (DCM) patients. In the human heart, SLM2 binds to important transcripts of sarcomere constituents, such as those encoding myosin light chain 2 (MYL2), troponin I3 (TNNI3), troponin T2 (TNNT2), tropomyosin 1/2 (TPM1/2), and titin (TTN). Mechanistically, SLM2 mediates intron retention, prevents exon exclusion, and thereby mediates alternative splicing of the mRNA regions encoding the variable proline-, glutamate-, valine-, and lysine-rich (PEVK) domain and another part of the I-band region of titin. In summary, SLM2 is a novel cardiac splicing regulator with essential functions for maintaining cardiomyocyte integrity by binding to and processing the mRNAs of essential cardiac constituents such as titin.

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Section: Introductionmentioning

confidence: 99%

SLM2 Is a Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy

Boeckel

Möbius-Winkler²,

Müller

et al. 2021

Genomics, Proteomics &Amp; Bioinformatics

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“…Like MYH6, MYH7 is a protein found as a component of the myosin protein in the heart, and having a mutation is associated with an enlarged heart and other CVDs. 120,121 A total of 753 mutations were mapped onto the MYH7 sequence (Figure 5X): two are missense mutations, 10 are splice mutations, 494 are intron mutations, 63 are silent mutations, 180 are 5′ flank mutations and four are 3′ UTR mutations. Of these mutations, one has medium impact, one has high impact, one is tolerated, one is deleterious and two are possibly damaging.…”

Section: Myh7mentioning

confidence: 99%

Investigating genes associated with cardiovascular disease among heart failure patients for translational research and precision medicine

Ahmed

Zeeshan

Persaud

et al. 2023

Clinical and Translational Dis

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Background Cardiovascular disease (CVD) is a leading cause of premature mortality in the United States and the world. CVD comprises several complex and mostly heritable conditions, which range from myocardial infarction to congenital heart disease. The risk factors contributing to the development of CVD and response to therapy in an individual patient are highly variable. Here, we report our findings from an integrative analysis of gene expression, disease‐causing gene variants and associated phenotypes among CVD populations, with a focus on high‐risk heart failure (HF) patients. Methods We built a cohort using electronic health records of consented patients with available samples and then performed high‐throughput whole genome and RNA sequencing of key genes responsible for HF and other CVD pathologies. Our in‐depth gene expression analysis revealed differentially expressed genes associated with HF and other CVDs. We performed a variant analysis of whole genome sequence data of CVD patients and identified genes with altered gene expression with functional and non‐functional mutations in these genes. Results Our results highlight the importance of investigating the mechanisms of CVD progression through multi‐omics datasets. Next, we performed splice mutation and variant distribution analysis of genes associated with HF and other CVD. We implemented Jensen–Shannon divergence (JSD)‐based method and identified HBA1, FADD, ADRB2, NPPB, ADRB1, ADB and NPPC genes with the greatest variance based on their JSD scores. Our study provided evidence that applying integrative data analysis approach involving genomics and transcriptomics data will not only help understand the pathophysiology of CVD diseases but also reduce heterogeneity in disease subtypes.

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“…The samples belonged to a hospital in Hyderabad and common SNPs were found in exons 7, 12, 19 and 20 in DCM and HCM conditions. These SNPs when present in homozygous conditions gave rise to DCM [ 137 ]. Similarly, in another work, they aimed to reveal ACE indel (I/D) mutation-associated cardiomyopathic development in the Indian population showing reduced LVEF in DCM patients, which pointed towards the influence of ID genotype on cardiomyopathic phenotype [ 138 ].…”

Section: Epidemiological Studies In India On Dcmmentioning

confidence: 99%

A Comprehensive Outlook on Dilated Cardiomyopathy (DCM): State-Of-The-Art Developments with Special Emphasis on OMICS-Based Approaches

Sarohi

Srivastava

2022

JCDD

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Dilated cardiomyopathy (DCM) remains an enigmatic cardiovascular disease (CVD) condition characterized by contractile dysfunction of the myocardium due to dilation of the ventricles. DCM is one of the major forms of CVD contributing to heart failure. Dilation of the left or both ventricles with systolic dysfunction, not explained by known causes, is a hallmark of DCM. Progression of DCM leads to heart failure. Genetic and various other factors greatly contribute to the development of DCM, but the etiology has still remained elusive in a large number of cases. A significant number of studies have been carried out to identify the genetic causes of DCM. These candidate-gene studies revealed that mutations in the genes of the fibrous, cytoskeletal, and sarcomeric proteins of cardiomyocytes result in the development of DCM. However, a significant proportion of DCM patients are idiopathic in nature. In this review, we holistically described the symptoms, causes (in adults and newborns), genetic basis, and mechanistic progression of DCM. Further, we also summarized the state-of-the-art diagnosis, available biomarkers, treatments, and ongoing clinical trials of potential drug regimens. DCM-mediated heart failure is on the rise worldwide including in India. The discovery of biomarkers with a better prognostic value is the need of the hour for better management of DCM-mediated heart failure patients. With the advent of next-generation omics-based technologies, it is now possible to probe systems-level alterations in DCM patients pertaining to the identification of novel proteomic and lipidomic biomarkers. Here, we also highlight the onset of a systems-level study in Indian DCM patients by applying state-of-the-art mass-spectrometry-based “clinical proteomics” and “clinical lipidomics”.

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Genetic variations of β-MYH7 in hypertrophic cardiomyopathy and dilated cardiomyopathy

Cited by 15 publications

References 13 publications

SLM2 Is a Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy

SLM2 Is a Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy

Investigating genes associated with cardiovascular disease among heart failure patients for translational research and precision medicine

A Comprehensive Outlook on Dilated Cardiomyopathy (DCM): State-Of-The-Art Developments with Special Emphasis on OMICS-Based Approaches

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