Genetic Insights Into Primary Restrictive Cardiomyopathy

Brodehl, Andreas; Gerull, Brenda

doi:10.20944/preprints202203.0265.v1

Cited by 13 publications

(3 citation statements)

References 169 publications

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“…In 2003, Mogensen and colleagues firmly established that troponin I mutations were etiological causes of RCM (Mogensen et al, 2003). The mutations in genes encoding sarcomeric and cytoskeletal proteins, including ACTC, ACTC1, ACTN2, BAG3, CRYAB, DCBLD2, DES, FLNC, LMNA, MYH, MYH7, MYL2, MYL3, β-MHC, MYBPC3, MYPN, TMEM87B, TNNI3, TNNT2, TNNC1, TPM1 and TTN, that have been reported to be etiologically linked to RCM (Muchtar et al, 2017;Cimiotti et al, 2021;Brodehl & Gerull, 2022). All known RCM genes are localized on autosomes and in most cases, the mutations are inherited as autosomal dominant mode or occur as de novo mutations.…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing identifies variants in the \(\textit{TNNI3}\) gene in vietnamese patient with restrictive cardiomyopathy - a case report

Lien,

Nguyen,

et al. 2024

AJB

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Restrictive cardiomyopathy (RCM) is a rare heart muscle disease in which the heart wall is rigid leading to diastolic dysfunction caused by abnormal elastic properties of the myocardium and/or intercellular matrix. The prognosis is generally poor, and RCM has a high mortality rate in pediatric patients. There are no curative treatments for RCM, so cardiac transplantation is the only effective treatment. Diagnosis RCM, clinical diagnosis can be challenging because clinical presentations and imaging manifestations of RCM are similar to other cardiomyopathies so it requires other specific diagnoses. Currently, pathogenic mutations in 22 different genes have been identified in patients with RCM. Identifying mutations in these genes helps discriminate RCM from other cardiomyopathies. Besides, next-generation sequencing (including whole genome sequencing, whole exome sequencing,...) has provided an effective tool for simultaneously analyzing mutations in many different genes. In this study, we conducted sequencing of the entire gene coding region (WES) in the patient and identified a compound heterozygote variants (c.289C>G, p.Arg97Gly and c.433C>T, p.Arg145Trp) in the TNNI3 gene. These variants were inherited from the patient's father and mother, who were heterozygous variant carriers. These variants were also identified as the pathogenic variants in the ClinVar database (accession number VCV001331910.2 and VCV000012426.28, respectively) and were the cause of the patient's disease. Our results suggest that WES can be used to definitively diagnose the genetic variants associated with RCM and show that genetic screening is essential for families of RCM patients.

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Section: Introductionmentioning

confidence: 99%

Whole exome sequencing identifies variants in the \(\textit{TNNI3}\) gene in vietnamese patient with restrictive cardiomyopathy - a case report

Lien,

Nguyen,

et al. 2024

AJB

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“…In arrhythmogenic cardiomyopathy (ACM), most pathogenic variants are in genes encoding desmosomal proteins such as Plakoglobin (JUP) (13, 41), DSP (48), Plakophilin-2 (PKP2), Desmoglein-2 (DSG2) and Desmocollin-2 (DSC2) (4,51,67). Finally, inherited restrictive cardiomyopathies are caused by mutations in sarcomeric genes such as cardiac troponin I, and less commonly by mutations in Desmin (DES) and Filamin C (FLNC) (7). It is worth noting that although cardiomyopathies are classified based on phenotypes manifested in the general population, the pathogenic mechanisms and phenotypic features among the various types of cardiomyopathies can overlap to a significant degree.…”

Section: Introductionmentioning

confidence: 99%

The role of noncoding genetic variants in cardiomyopathy

Htet,

Lei,

Bajpayi

et al. 2023

Front. Cardiovasc. Med.

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Cardiomyopathies remain one of the leading causes of morbidity and mortality worldwide. Environmental risk factors and genetic predisposition account for most cardiomyopathy cases. As with all complex diseases, there are significant challenges in the interpretation of the molecular mechanisms underlying cardiomyopathy-associated genetic variants. Given the technical improvements and reduced costs of DNA sequence technologies, an increasing number of patients are now undergoing genetic testing, resulting in a continuously expanding list of novel mutations. However, many patients carry noncoding genetic variants, and although emerging evidence supports their contribution to cardiac disease, their role in cardiomyopathies remains largely understudied. In this review, we summarize published studies reporting on the association of different types of noncoding variants with various types of cardiomyopathies. We focus on variants within transcriptional enhancers, promoters, intronic sites, and untranslated regions that are likely associated with cardiac disease. Given the broad nature of this topic, we provide an overview of studies that are relatively recent and have sufficient evidence to support a significant degree of causality. We believe that more research with additional validation of noncoding genetic variants will provide further mechanistic insights on the development of cardiac disease, and noncoding variants will be increasingly incorporated in future genetic screening tests.

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“…Genetic and non-genetic factors contribute to RCM. Pathogenic mutations in over 19 different genes related to RCM have been identified (6). The major mutations are found in genes encoding for sarcomere proteins, such as cardiac troponins I (TNNI3), alpha tropomyosin (TPM1), titin (TTN), and so on (7).…”

Section: Introductionmentioning

confidence: 99%

Case report: Rare restrictive cardiomyopathy with ventricular fibrillation as initial symptom rescued by automatic external defibrillator in a pediatric patient

Chen

Qin

et al. 2022

Front. Cardiovasc. Med.

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Restrictive cardiomyopathy (RCM) is a rare form of heart muscle disease with poor prognosis. Its primary manifestations were caused by systemic or pulmonary circulation congestion. Here, we reported a case of RCM with ventricular fibrillation as initial symptom in a 7-year-old boy. The child suffered cardiac and respiratory arrest suddenly while exercising at school and immediately was given external chest compression and defibrillation by the school’s equipped automatic external defibrillator (AED). The rescue was successful. At the time of the AED discharge, his electrocardiogram (ECG) indicated ventricular fibrillation. Upon further examination, the echocardiogram revealed enlarged bilateral atria, decreased diastolic function and normal ventricular thickness. Genetic analysis identified a heterozygous missense mutation [c.611(exon8)G>A,p.R204H] of TNNI3 in the proband boy. This case contributes to our understanding of RCM in children and emphasizes the importance of having AEDs available in public places.

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Genetic Insights Into Primary Restrictive Cardiomyopathy

Cited by 13 publications

References 169 publications

Whole exome sequencing identifies variants in the \(\textit{TNNI3}\) gene in vietnamese patient with restrictive cardiomyopathy - a case report

Whole exome sequencing identifies variants in the \(\textit{TNNI3}\) gene in vietnamese patient with restrictive cardiomyopathy - a case report

The role of noncoding genetic variants in cardiomyopathy

Case report: Rare restrictive cardiomyopathy with ventricular fibrillation as initial symptom rescued by automatic external defibrillator in a pediatric patient

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