Left Dominant Arrhythmogenic Cardiomyopathy Caused by a Novel Nonsense Mutation in Desmoplakin

Navarro-Manchón, Josep; Fernández, E.; Igual, B.; Asimaki, Angeliki; Syrris, Petros; Osca, Joaquín; Salvador, Antonio; Zorio, Esther

doi:10.1016/j.rec.2010.10.020

Cited by 10 publications

(8 citation statements)

References 16 publications

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“…There are several main findings. LV dysfunction and LV structural involvement are significantly more common in carriers of non-missense mutations, in agreement with previous suggestions (5,6,17,19,22). There is no difference between carriers of missense and non-missense mutations as arrhythmic events are concerned, at variance with previous reports (10,22,23).…”

Section: Discussionsupporting

confidence: 91%

“…Even in the initial clinical descriptions of DSP mutation carriers (4), only the carriers of non-missense mutations had an early LV involvement (17). This observation has been further replicated, with small numbers, in other studies reporting on single patients (17,19) or on a few more than a dozen missense and non-missense DSP mutation carriers within a population of genotyped ARVC probands (6).…”

Section: Accepted Manuscriptmentioning

confidence: 57%

“…Recently, DSP mutations have been often associated with predominant LV or biventricular involvement (4,6,8,11,(16)(17)(18)(19)(20)(21)(22). It has been suggested that, among all DSP mutations, those which are non-missense are often associated with left dominant or biventricular forms (6,17).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Three statements, reported in the literature, are of interest but are based on very small numbers. One is that DSP mutations seem to be more often associated with a predominant LV phenotype or biventricular involvement (4,8,(16)(17)(18)(19)(20)(21); another is that DSP mutations (4,11), especially truncations (22), are associated with a much more penetrant phenotype with SCD often as first disease manifestation; the third, and more controversial, is that ARVC missense mutations could be more severe than non-missense mutations (10,23).…”

Section: Introductionmentioning

confidence: 99%

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Desmoplakin missense and non-missense mutations in arrhythmogenic right ventricular cardiomyopathy: Genotype-phenotype correlation

Castelletti

Vischer

Syrris³

et al. 2017

International Journal of Cardiology

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For ARVC patients, both missense and non-missense DSP mutations carry a high arrhythmic risk. Non-missense mutations are specifically associated with left-dominant forms. The presence of DSP non-missense mutations should alert to the likely development of LV dysfunction. These findings highlight the clinical relevance of genetic testing even after the clinical diagnosis of ARVC and the growing clinical impact of genetics.

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Section: Discussionsupporting

confidence: 91%

Section: Accepted Manuscriptmentioning

confidence: 57%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Desmoplakin missense and non-missense mutations in arrhythmogenic right ventricular cardiomyopathy: Genotype-phenotype correlation

Castelletti

Vischer

Syrris³

et al. 2017

International Journal of Cardiology

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“…reported a case of a 24‐year‐old man with acute myocarditis as the first presentation of AC, and a novel DSP variant was reported. Navarro‐Manchón et al . described a case of a Spanish family, where a 36‐year‐old male presented with atypical chest pain and CMR findings suggestive of myocarditis.…”

Section: Discussionmentioning

confidence: 99%

Monozygotic twins with myocarditis and a novel likely pathogenic desmoplakin gene variant

et al. 2020

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Myocarditis most often affects otherwise healthy athletes and is one of the leading causes of sudden death in children and young adults. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder with increased risk for paroxysmal ventricular arrhythmias and sudden cardiac death. The clinical picture of myocarditis and ARVC may overlap during the early stages of cardiomyopathy, which may lead to misdiagnosis. In the literature, we found several cases that presented with episodes of myocarditis and ended up with a diagnosis of arrhythmogenic cardiomyopathy, mostly of the left predominant type. The aim of this case presentation is to shed light upon a possible link between myocarditis, a desmoplakin (DSP) gene variant, and ARVC by describing a case of male monozygotic twins who presented with symptoms and signs of myocarditis at 17 and 18 years of age, respectively. One of them also had a recurrent episode of myocarditis. The twins and their family were extensively examined including electrocardiograms (ECG), biochemistry, multimodal cardiac imaging, myocardial biopsy, genetic analysis, repeated cardiac magnetic resonance (CMR) and echocardiography over time. Both twins presented with chest pain, ECG with slight ST-T elevation, and increased troponin T levels. CMR demonstrated an affected left ventricle with comprehensive inflammatory, subepicardial changes consistent with myocarditis. The right ventricle did not appear to have any abnormalities. Genotype analysis revealed a nonsense heterozygous variant in the desmoplakin (DSP) gene [NM_004415.2:c.2521_2522del (p.Gln841Aspfs*9)] that is considered likely pathogenic and presumably ARVC related. There was no previous family history of heart disease. There might be a common pathophysiology of ARVC, associated with desmosomal dysfunction, and myocarditis. In our case, both twins have an affected left ventricle without any right ventricular involvement, and they are carriers of a novel DSP variant that is likely associated with ARVC. The extensive inflammation of the LV that was apparent in the CMR may or may not be the primary event of ARVC. Nevertheless, our data suggest that irrespective of a possible link here to ARVC, genetic testing for arrhythmogenic cardiomyopathy might be advisable for patients with recurrent myocarditis associated with a family history of myocarditis.

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Importance of cardiac magnetic resonance findings in the diagnosis of left dominant arrythmogenic cardiomyopathy

Feliu

Moscicki

Carrillo

et al. 2020

Revista Española de Cardiología (English Edition)

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Left Dominant Arrhythmogenic Cardiomyopathy Caused by a Novel Nonsense Mutation in Desmoplakin

Cited by 10 publications

References 16 publications

Desmoplakin missense and non-missense mutations in arrhythmogenic right ventricular cardiomyopathy: Genotype-phenotype correlation

Desmoplakin missense and non-missense mutations in arrhythmogenic right ventricular cardiomyopathy: Genotype-phenotype correlation

Monozygotic twins with myocarditis and a novel likely pathogenic desmoplakin gene variant

Importance of cardiac magnetic resonance findings in the diagnosis of left dominant arrythmogenic cardiomyopathy

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