Dilated cardiomyopathy: from epidemiologic to genetic phenotypes

Reichart, Daniel; Magnussen, Christina; Zeller, Tanja; Blankenberg, Stefan

doi:10.1111/joim.12944

Cited by 144 publications

(158 citation statements)

References 95 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…DCM is a common cause of HF and cardiac transplantation in young adults, with an estimated prevalence of 1:2500 and up to 1:250-400 [30][31][32], and is characterized by ventricular dilatation and contractile dysfunction. While it is clear that DCM can be determined by both genetic and non-genetic factors, the mechanisms underlying its development remain poorly understood.…”

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Metabolic Alterations in Inherited Cardiomyopathies

Sacchetto

Sequeira

Bertero

et al. 2019

JCM

View full text Add to dashboard Cite

The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand of cardiomyocytes, involving an intricate network of pathways regulating the metabolic flux of substrates. The failure of these processes results in structural and functional deficiencies of the cardiac muscle, including inherited cardiomyopathies. These genetic diseases are characterized by cardiac structural and functional anomalies in the absence of abnormal conditions that can explain the observed myocardial abnormality, and are frequently associated with heart failure. Since their original description, major advances have been achieved in the genetic and phenotype knowledge, highlighting the involvement of metabolic abnormalities in their pathogenesis. This review provides a brief overview of the role of mitochondria in the energy metabolism in the heart and focuses on metabolic abnormalities, mitochondrial dysfunction, and storage diseases associated with inherited cardiomyopathies.

show abstract

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Metabolic Alterations in Inherited Cardiomyopathies

Sacchetto

Sequeira

Bertero

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…To elucidate the possible genetic mechanisms of KD pathogenesis, a dilated cardiomyopathy, rare variants of DCM-causative genes were measured in accordance with minor allele frequency (MAF) below 0.1% in the ExAC and the database for the 1000 Genomes Project [12,13]. There are various rare variants of DCM-causative genes in KD patients as follows: 34 rare variants in TTN (n = 34), 20 in OBSCN (n = 20), 4 in LAMA4 (n = 4), 2 in MYBPC3 (n = 2), 2 in VCL (n = 2), 3 in FHL2 (n = 3), 3 in ZBTB17 (n = 3), 2 in RBM20 (n = 2), 2 in ANKRD1 (n = 2), 2 in KCNQ1 (n = 2), 4 in DMD (n = 4), 2 in MYPN (n = 2), x in MYH7 (n = 2), 2 in BRAF (n = 2), 4 in FLNC (n = 4), 1 in MYH6 (n = 1), 3 in SYNM (n = 3), 2 in RYR2 (n = 2), 1 in ABCC9 (n = 1), 1 in DSC2 (n = 1), 1 in FKRP (n = 1), 1 in FKTN (n = 1), 2 in LDB3 (n = 2), 2 in SCN5A (n = 2), 1 in TXNRD2 (n = 1), 1 in SOS1 (n = 1), 1 in MURC (n = 1), 1 in DSG2 (n = 1) as shown in Supplementary Table S2 and Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…The effective treatments used in KD are not available so far. Fortunately, an in-depth understanding of the molecular mechanisms underlying DCM opens the door to explore Keshan disease [12,13]. As for KD, we identified various DCM-causative genes, encoding for diverse proteins of the sarcomere ( MYH6, MYH7, MYBPC3 , and MYPN ), cytoskeleton ( TTN, ACTN2, LDB3, SYNM, DMD, FHL2, FKTN, VCL, FLNC, MURC , and NEBL ), desmosomes ( DSP, DSC2, DSG2, PKP2 , and CTNNA3 ), nucleus ( RBM20, ANKRD1, PRDM16, ZBTB17, ALPK3 , and LRRC10 ), ion channel ( SCN5A, ABCC9 , and KCNQ1 ), extracellular matrix ( LAMA2 , and LAMA4 ), and mitochondria ( TXNRD2 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative analyses identify potential key genes and pathways in Keshan disease using whole-exome sequencing

Huang

Zheng

Luo

et al. 2021

Preprint

View full text Add to dashboard Cite

Keshan disease (KD), an endemic heart disease with multifocal necrosis and replacement fibrosis of the myocardium, is still a nightmare situation for human health. However, molecular mechanism in the pathogenesis of KD remains unclear. Herein, blood samples were collected from 68 KD patients and 100 controls, and we systematically analyzed mutation profiles using whole-exome sequencing (WES). Causative genes of dilated cardiomyopathy (DCM), gene-based burden analysis, disease and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. Of the 98 DCM-causative genes, 106 rare variants in 28 genes were detected in KD patients with minor allele frequency (MAF) < 0.001. Gene-based burden analysis, PPI network analysis, and automated Phenolyzer analysis were performed to prioritize 199 candidate genes, which combined with 98 DCM-causative genes, and reference genes from gene microarray or proteomics in KD. Then, 19 candidate pathogenic genes were selected, and 9 candidate genes were identified using PPI analysis, including HIF1A, GART, ALAD, VCL, DTNA, NEXN, INPPL1, NOS3, and JAK2. The 199 candidate genes were further analyzed using disease enrichment with CTD database and PPI analysis, and 21 candidate genes were identified. By combining with disease enrichment and PPI analysis, 7 Selenium (Se)-related genes were further identified, including ALAD, RBM10, GSN, GGT1, ADD1, PARP1, and NOS3. Based on the gene function and data validation, NEXN, TAF1C, FUT4, ALAD, ZNF608, and STX2 were the most likely pathogenic genes in KD. Notably, ALAD is the only candidate pathogenic gene identified by four different analyses, and its homozygous mutant mice could affect heart development and cause death. Keywords: Keshan disease, dilated cardiomyopathy, whole-exome sequencing, gene-based burden analysis, automated Phenolyzer analysis

show abstract

“…), trauma, and endocrine and metabolic disorders 101112 . The incidence of DCM is reported to be 5-7 cases per 100 000 people per year 13 . Previous reports revealed that the prevalence of DCM was 36.5 cases per 100,000 people per year 14 .…”

Section: Introductionmentioning

confidence: 99%

Disorganization of Intercalated Discs in Dilated Cardiomyopathy

Ito

Yoshida

Masuda³

et al. 2021

Preprint

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility. The clinical and pathological diagnosis of DCM is difficult, and other cardiac diseases must be ruled out. Several studies have reported pathological findings that are characteristic of DCM, including cardiomyocyte atrophy, nuclear pleomorphism, and interstitial fibrosis, but none of these findings are DCM-specific. In this study, we examined the morphological differences in ICDs between three groups of patients, a DCM group, a chronic heart failure group, and a control group. A total of 21 autopsy cases, including five DCM cases, eight CHF cases and eight control cases, were retrieved from the archives of the Department of Pathology at Akita University, Japan. The morphological differences were examined using multiple methods: macroscopic examination, light microscopy, immunohistochemistry, electron microscopy, and gene expression analyses. We observed disorganized intercalated discs (ICDs), clearly illustrated by N-cadherin immunostaining in the DCM group. “Reduction of N-cadherin immunostaining intensity” and “ICD scattering” was DCM-specific. The results suggest that disorganized ICDs contribute to the development of DCM, and that N-cadherin immunostaining is useful for determining the presence of disorganized ICDs and for the pathological diagnosis of DCM.

show abstract

Dilated cardiomyopathy: from epidemiologic to genetic phenotypes

Cited by 144 publications

References 95 publications

Metabolic Alterations in Inherited Cardiomyopathies

Metabolic Alterations in Inherited Cardiomyopathies

Integrative analyses identify potential key genes and pathways in Keshan disease using whole-exome sequencing

Disorganization of Intercalated Discs in Dilated Cardiomyopathy

Contact Info

Product

Resources

About