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Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy

Syrris, P; Ward, D; Asimaki, A; Sen-Chowdhry, S; Ebrahim, HY; Evans, A; Hitomi, N; ... McKenna, WJ; + view all (2006) Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy. CIRCULATION , 113 (3) 356 - 364. 10.1161/CIRCULATIONAHA.105.561654. Green open access

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Abstract

Background - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder characterized by loss of cardiomyocytes and their replacement by adipose and fibrous tissue. It is considered a disease of cell adhesion because mutations in desmosomal genes, desmoplakin and plakoglobin, have been implicated in the pathogenesis of ARVC. In a recent report, mutations in plakophilin-2, a gene highly expressed in cardiac desmosomes, have been shown to cause ARVC.Methods and Results - We investigated 100 white patients with ARVC for mutations in plakophilin-2. Nine different mutations were identified by direct sequencing in 11 cases. Five of these mutations are novel (A733fsX740, L586fsX658, V570fsX576, R413X, and P533fsX561) and predicted to cause a premature truncation of the plakophilin-2 protein. Family studies showed incomplete disease expression in mutation carriers and identified a number of individuals who would be misdiagnosed with the existing International Task Force and modified diagnostic criteria for ARVC.Conclusions - In this study, we provide new evidence that mutations in the desmosomal plakophilin-2 gene can cause ARVC. A systematic clinical evaluation of mutation carriers within families demonstrated variable phenotypic expression, even among individuals with the same mutation, and highlighted the need for a more accurate set of diagnostic criteria for ARVC.

Type: Article
Title: Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCULATIONAHA.105.561654
Keywords: arrhythmia, cardiomyopathy, death, sudden, diagnosis, genetics, WOOLLY HAIR, RECESSIVE MUTATION, FRAGILITY SYNDROME, DESMOSOMAL PLAQUE, SKIN FRAGILITY, SUDDEN-DEATH, DYSPLASIA, GENE, DIAGNOSIS, PROTEINS
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/8624
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