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

Article

关键词: WOOLLY HAIR;    RECESSIVE MUTATION;    FRAGILITY SYNDROME;    DESMOSOMAL PLAQUE;    SKIN FRAGILITY;    SUDDEN-DEATH;    DYSPLASIA;    GENE;    DIAGNOSIS;    PROTEINS;   

DOI  :  10.1161/CIRCULATIONAHA.105.561654

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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