Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters

Otterspoor, Luuk C.; Reichert, Constant L.A.; Bhuiyan, Zahurul A.; Wilde, Arthur A.M.; Hauer, Richard N.W.

doi:10.1007/bf03086013

Cited by 7 publications

(2 citation statements)

References 20 publications

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“…Furthermore, most patients harboring a mutation in ARVC-associated genes present with ARVC by 30 years of age although homozygous patients ( e.g ., Naxos disease) show 100% penetrance by adolescence 42 . Long-term cardiac monitoring by EKG, Holter monitoring, echocardiography, and exercise stress test is recommended for the patients harboring mutations in ARVC-associated genes as well as those presenting with PPK and hair shaft anomalies with unknown genotype; however, it was reported that only 2.3% of patients with such cutaneous phenotypes receive relevant cardiac monitoring 41 , 42 . In this context, because of age-dependent penetrance and the young age of our patients, further studies and close follow-up are needed, including cardiological monitoring of family members at risk.…”

Section: Discussionmentioning

confidence: 99%

Arrhythmogenic right ventricular cardiomyopathy in patients with biallelic JUP-associated skin fragility

Vahidnezhad

Youssefian

Faghankhani

et al. 2020

Sci Rep

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Arrhythmogenic right ventricular cardiomyopathy (ARVC), with skin manifestations, has been associated with mutations in JUP encoding plakoglobin. Genotype–phenotype correlations regarding the penetrance of cardiac involvement, and age of onset have not been well established. We examined a cohort of 362 families with skin fragility to screen for genetic mutations with next-generation sequencing-based methods. In two unrelated families, a previously unreported biallelic mutation, JUP: c.201delC; p.Ser68Alafs*92, was disclosed. The consequences of this mutation were determined by expression profiling both at tissue and ultrastructural levels, and the patients were evaluated by cardiac and cutaneous work-up. Whole-transcriptome sequencing by RNA-Seq revealed JUP as the most down-regulated gene among 21 skin fragility-associated genes. Immunofluorescence showed the lack of plakoglobin in the epidermis. Two probands, 2.5 and 22-year-old, with the same homozygous mutation, allowed us to study the cross-sectional progression of cardiac involvements in relation to age. The older patient had anterior T wave inversions, prolonged terminal activation duration (TAD), and RV enlargement by echocardiogram, and together with JUP mutation met definite ARVC diagnosis. The younger patient had no evidence of cardiac disease, but met possible ARVC diagnosis with one major criterion (the JUP mutation). In conclusion, we identified the same biallelic homozygous JUP mutation in two unrelated families with skin fragility, but cardiac findings highlighted age-dependent penetrance of ARVC. Thus, young, phenotypically normal patients with biallelic JUP mutations should be monitored for development of ARVC.

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Section: Discussionmentioning

confidence: 99%

Arrhythmogenic right ventricular cardiomyopathy in patients with biallelic JUP-associated skin fragility

Vahidnezhad

Youssefian

Faghankhani

et al. 2020

Sci Rep

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“…Li et al 2011Garcia-Gras et al 2006 Munkholm et al 2012Asimaki et al 2007 Huang et al 2008 Plakophilin-2Gerull et al 2004Otterspoor et al 2007 Antoniades et al 2006Aneq et al 2011Awad et al 2006bAdachi and Isobe 2011Calkins 2006Gandjbakhch et al 2011Dalal et al 2006Gehmlich et al 2011aKannankeril et al 2006Kapplinger et al 2011Nagaoka et al 2006Larsen et al 2011Syrris et al 2006aNakajima et al 2011van Tintelen et al 2006Ostrowska Dahlgren et al 2011 Pamuru et al 2011Joshi-Mukherjee et al 2008Paul et al 2011Lahtinen et al 2008van der Zwaag et al 2011aRam and Van Wagoner 2008Zhang et al 2012Tandri et al 2008 Bhuiyan et al 2009den Haan et al 2009Fidler et al 2009Hall et al 2009Qiu et al 2009Watkins et al 2009Wu et al 2009 Christensen et al 2010aChristensen et al 2010b…”

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confidence: 99%

Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases

Rickelt

Pieperhoff

2012

Cell Tissue Res

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In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar regions (intercalated disks) of mature mammalian cardiomyocytes. These molecules, apparently together with some specific cytoskeletal proteins, are components of (or interact with) composite junctions. Composite junctions contain the amalgamated fusion products of the molecules that, in other cell types and tissues, occur in distinct separate junctions, i.e. desmosomes and adherens junctions. As the pertinent literature is still in an expanding phase and is obviously becoming important for various groups of researchers in basic cell and molecular biology, developmental biology, histology, physiology, cardiology, pathology and genetics, the relevant references so far recognized have been collected and are presented here in the following order: desmocollin-2 (Dsc2, DSC2), desmoglein-2 (Dsg2, DSG2), desmoplakin (DP, DSP), plakoglobin (PG, JUP), plakophilin-2 (Pkp2, PKP2) and some non-desmosomal proteins such as transmembrane protein 43 (TMEM43), ryanodine receptor 2 (RYR2), desmin, lamins A and C, striatin, titin and transforming growth factor-β3 (TGFβ3), followed by a collection of animal models and of reviews, commentaries, collections and comparative studies.

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The junctions that don’t fit the scheme: special symmetrical cell-cell junctions of their own kind

et al. 2009

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Immunocytochemical, electron-, and immunoelectron-microscopical studies have revealed that, in addition to the four major "textbook categories" of cell-cell junctions (gap junctions, tight junctions, adherens junctions, and desmosomes), a broad range of other junctions exists, such as the tiny puncta adhaerentia minima, the taproot junctions (manubria adhaerentia), the plakophilin-2-containing adherens junctions of mesenchymal or mesenchymally derived cell types including malignantly transformed cells, the composite junctions (areae compositae) of the mature mammalian myocardium, the cortex adhaerens of the eye lens, the interdesmosomal "sandwich" or "stud" junctions in the subapical layers of stratified epithelia and the tumors derived therefrom, and the complexus adhaerentes of the endothelial and virgultar cells of the lymph node sinus. On the basis of their sizes and shapes, other morphological criteria, and their specific molecular ensembles, these junctions and the genes that encode them cannot be subsumed under one of the major categories mentioned above but represent special structures in their own right, appear to serve special functions, and can give rise to specific pathological disorders.

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Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters

Cited by 7 publications

References 20 publications

Arrhythmogenic right ventricular cardiomyopathy in patients with biallelic JUP-associated skin fragility

Arrhythmogenic right ventricular cardiomyopathy in patients with biallelic JUP-associated skin fragility

Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases

The junctions that don’t fit the scheme: special symmetrical cell-cell junctions of their own kind

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