Arrhythmogenic right ventricular cardiomyopathy

Cho, Yongkeun

doi:10.1002/joa3.12012

Cited by 13 publications

(17 citation statements)

References 89 publications

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“…NGS sequencing analysis helped physicians to establish the postmortem diagnosis of arrhythmogenic cardiomyopathy by the finding of a pathogenic mutation in the PKP2 gene. Clinical diagnosis of ACM may be challenging, and therefore, predictive genetic testing may offer valid means to help and identify subjects at risk, before the presence of phenotypical traits, before the onset of early warning symptoms, and ultimately prior to malignant arrhythmic events (23)(24)(25). In this case, the discovery of a putative disease-causing variant in the PKP2 gene raised doubts about the initial cause of death reported in the first autopsy and helped us convince the family to consent to reassessment of the autopsy findings.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Variability of a Pathogenic PKP2 Mutation in an Italian Family Affected by Arrhythmogenic Cardiomyopathy and Juvenile Sudden Death: Considerations From Molecular Autopsy to Sport Restriction

Leone

Palumbo

Saenen

et al. 2021

Front. Cardiovasc. Med.

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Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder with an estimated prevalence between 1:2,000 and 1:5,000 and is characterized by the fibrofatty replacement of cardiomyocytes that predisposes to malignant arrhythmias, heart failure, and sudden cardiac death. The diagnosis is based on the 2010 Task Force Criteria including family history, electrocardiographic traits and arrhythmogenic pattern, specific gene mutations, and structural and/or histological abnormalities. Most ACMs display an autosomal dominant mode of inheritance often with incomplete penetrance and variable expressivity. Genetic screening of patients with ACM identifies pathogenic or likely pathogenic variants, prevalently in genes encoding the cardiac desmosome (PKP2, DSP, DSC2, DSG2, and JUP) or less frequently in non-desmosomal genes (CTNNA3, PLN, TMEM43, RYR2, SCN5A, CDH2, and DES).Methods: In the present study, we performed molecular autopsy in a boy who died suddenly during physical exertion. In addition to post-mortem examination, a DNA sample was analyzed with next-generation sequencing (NGS).Results: The genetic analysis revealed the presence of pathogenic heterozygous c.314del (p.Pro105Leufs*7) frameshift variant in the PKP2 gene. Cascade screening of family members allowed us to identify 12 mutation carriers and to intervene on subjects at risk, many of whom were athletes.Conclusions: Molecular autopsy can establish cardiogenetic diagnosis and allow appropriate preventative measures in high-risk relatives.

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Section: Discussionmentioning

confidence: 99%

Phenotypic Variability of a Pathogenic PKP2 Mutation in an Italian Family Affected by Arrhythmogenic Cardiomyopathy and Juvenile Sudden Death: Considerations From Molecular Autopsy to Sport Restriction

Leone

Palumbo

Saenen

et al. 2021

Front. Cardiovasc. Med.

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“…This difference may be caused by different types of mutation as well as incomplete penetrance. So, it is difficult to confirm the diagnosis of ARVC based on the general clinical examination because of the nonspecific nature of the disease and the broad spectrum of phenotypic variations [26, 27]. The genetic analysis and sequencing may make some contributions to the diagnosis of ARVC.…”

Section: Discussionmentioning

confidence: 99%

Whole-Exome Sequencing Identified a De Novo Mutation of Junction Plakoglobin (p.R577C) in a Chinese Patient with Arrhythmogenic Right Ventricular Cardiomyopathy

Liu

Chen

et al. 2019

BioMed Research International

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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare and potentially life-threatening disorder of the heart. The clinical spectrum of ARVC includes myocyte loss and fibro-fatty tissue replacement. With the progress of ARVC, the patient can present serious ventricular arrhythmias, heart failure, and even sudden cardiac death. Previous studies have demonstrated that desmosomes and intermediate junctions play a crucial role in the generation and development of ARVC. In this study, we enrolled a Chinese patient with suspicious ARVC. The patient suffered from right ventricular enlargement and less thickening of right ventricular wall. ECG record showed an epsilon wave. However, there was no obvious symptom in his parents. After whole-exome sequencing and data filtering, we identified a de novo mutation (c.1729C>T/p.R577C) of junction plakoglobin (JUP) in this patient. Bioinformatics programs predicted that this mutation was deleterious. Western blot revealed that, compared to cells transfected with WT plasmids, the expressions of desmoglein 2 (DSG2) and Connexin 43 were decreased overtly in cells transfected with the mutant plasmid. Previous studies have proven that the reduction of DSG2 and Connexin 43 may disturb the stability of desmosomes. In this research, we reported a novel de novo mutation (c.1729C>T/p.R577C) of JUP in a Chinese patient with suspicious ARVC. Functional research further confirmed the pathogenicity of this novel mutation. Our study expanded the spectrum of JUP mutations and may contribute to the genetic diagnosis and counseling of patients with ARVC.

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“…Arrhythmogenic right ventricular dysplasia, now known as arrhythmogenic right ventricular cardiomyopathy (ARVC), is identified as an autosomal dominant genetic condition in about 50% of cases with variable penetrance first described in 1982 [1,2]. Although rare, autosomal recessive forms such as Carvajal syndrome and Naxos disease have also been described.…”

Section: Introductionmentioning

confidence: 99%

Arrhythmogenic Right Ventricular Cardiomyopathy: The Role of Genetics in Diagnosis, Management, and Screening

et al. 2022

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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a predominantly autosomal dominant genetic condition in which fibrous and fatty tissue infiltrate and replace healthy myocardial tissue. This uncommon yet debilitating condition can cause ventricular arrhythmias, cardiac failure, and sudden cardiac death. Management focuses primarily on prevention of syndrome sequelae in order to prevent morbidity and mortality. Genetic testing and screening in affected families, although utilized clinically, has not yet been incorporated in guidelines due to lack of larger studies and data. We aim herein to identify causative gene mutations, present advancements in diagnosis and management, and describe the role of genetic screening and counseling in patients with ARVC. With the advancement of genetic testing and therapy, diseases such as ARVC may become more accurately diagnosed and more effectively managed, ultimately significantly reducing morbidity and mortality.

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Arrhythmogenic right ventricular cardiomyopathy

Cited by 13 publications

References 89 publications

Phenotypic Variability of a Pathogenic PKP2 Mutation in an Italian Family Affected by Arrhythmogenic Cardiomyopathy and Juvenile Sudden Death: Considerations From Molecular Autopsy to Sport Restriction

Phenotypic Variability of a Pathogenic PKP2 Mutation in an Italian Family Affected by Arrhythmogenic Cardiomyopathy and Juvenile Sudden Death: Considerations From Molecular Autopsy to Sport Restriction

Whole-Exome Sequencing Identified a De Novo Mutation of Junction Plakoglobin (p.R577C) in a Chinese Patient with Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic Right Ventricular Cardiomyopathy: The Role of Genetics in Diagnosis, Management, and Screening

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