Clinical utility gene card for: arrhythmogenic right ventricular cardiomyopathy (ARVC)

Rijdt, Wouter P. te; Jongbloed, Jan D. H.; Boer, Rudolf A. de; Thiene, Gaetano; Basso, Cristina; Berg, Maarten P. van den; Tintelen, J. Peter van

doi:10.1038/ejhg.2013.124

Cited by 29 publications

(19 citation statements)

References 27 publications

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“…Sequence variants in 10 genes have been associated with ARVC, but the most commonly implicated genes are the desmosomal protein genes PKP2 (11–51% cases) and DSP (1–7%), DSG2 (3–20%), DSC2 (1–7%%) and JUP (0.5–16%). The mutation yield varies in different populations . Our overall desmosomal gene pathogenic variant yield is comparable with other Western European populations apart from the Netherlands, where a higher yield is found in PKP2 .…”

Section: Discussionsupporting

confidence: 71%

Phenotype‐driven molecular autopsy for sudden cardiac death

Cann¹,

Corbett

O'Sullivan³

et al. 2016

Clinical Genetics

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A phenotype-driven approach to molecular autopsy based in a multidisciplinary team comprising clinical and laboratory genetics, forensic medicine and cardiology is described. Over a 13 year period, molecular autopsy was undertaken in 96 sudden cardiac death cases. A total of 46 cases aged 1-40 years had normal hearts and suspected arrhythmic death. Seven (15%) had likely pathogenic variants in ion channelopathy genes [KCNQ1 (1), KCNH2 (4), SCN5A (1), RyR2(1)]. Fifty cases aged between 2 and 67 had a cardiomyopathy. Twenty-five had arrhythmogenic right ventricular cardiomyopathy (ARVC), 10 dilated cardiomyopathy (DCM) and 15 hypertrophic cardiomyopathy (HCM). Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1). Uptake of cascade screening in relatives was higher when a molecular diagnosis was made at autopsy. In three families, variants previously published as pathogenic were detected, but clinical investigation revealed no abnormalities in carrier relatives. With a conservative approach to defining pathogenicity of sequence variants incorporating family phenotype information and population genomic data, a molecular diagnosis was made in 15% of sudden arrhythmic deaths and 18% of cardiomyopathy deaths.

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Section: Discussionsupporting

confidence: 71%

Phenotype‐driven molecular autopsy for sudden cardiac death

Cann¹,

Corbett

O'Sullivan³

et al. 2016

Clinical Genetics

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“…Inheritance of ARVC is predominantly autosomal dominant, involving various genes encoding intercalated disc proteins, such as plakophilin and other proteins of the cardiac desmosomes . In addition, mutations in genes encoding non‐desmosomal proteins can be involved, including transforming growth factor‐β3, the cardiac ryanodine receptor, tmem43, titin, α‐catenin, desmin, and phospholamban . However, autosomal recessive transmission has also been described related to mutations in genes encoding plakoglobin and desmoplakin .…”

Section: Arrhythmogenic Right Ventricular Cardiomyopathymentioning

confidence: 99%

Sex differences in cardiomyopathies

Meyer

Meer

Tintelen

et al. 2014

European J of Heart Fail

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Cardiomyopathies are a heterogeneous group of heart muscle diseases with a variety of specific phenotypes. According to the contemporary European Society of Cardiology classification, they are classified into hypertrophic (HCM), dilated (DCM), arrhythmogenic right ventricular (ARVC), restrictive (RCM), and unclassified cardiomyopathies. Each class is aetiologically further categorized into inherited (familial) and non‐inherited (non‐familial) forms. There is substantial evidence that biological sex is a strong modulator of the clinical manifestation of these cardiomyopathies, and sex‐specific characteristics are detectable in all classes. For the clinician, it is important to know the sex‐specific aspects of clinical disease expression and the potential modes of inheritance or the hereditary influences underlying the development of cardiomyopathies, since these may aid in diagnosing such diseases in both sexes.

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“…AVC is most commonly inherited as an autosomal dominant trait with incomplete penetrance [5, 7, 75], although two autosomal recessive forms have been described [71]. To date, 15 genes have been reported to cause AVC ( Table 5 ) [4, 5, 7, 13, 76]. We and others demonstrated that compound and digenic heterozygosity is involved in AVC pathogenesis in up to 20% of cases and leads to a more severe disease [77, 78].…”

Section: Introductionmentioning

confidence: 99%

Inherited Cardiomyopathies

Towbin

2014

Circ J

163

148

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Cardiomyopathies, diseases of the heart muscle, are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease and, over the past two decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a “final common pathway” for that specific disorder but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The “final common pathways” for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM), the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy (DCM), and the desmosome in arrhythmogenic cardiomyopathy (AVC). Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and appears that any of these “final common pathways” can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described.

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Clinical utility gene card for: arrhythmogenic right ventricular cardiomyopathy (ARVC)

Cited by 29 publications

References 27 publications

Phenotype‐driven molecular autopsy for sudden cardiac death

Phenotype‐driven molecular autopsy for sudden cardiac death

Sex differences in cardiomyopathies

Inherited Cardiomyopathies

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