Article

Novel mutation of plakophilin-2 associated with arrhythmogenic right ventricular cardiomyopathy.

Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
Circulation Journal (impact factor: 3.77). 08/2006; 70(7):933-5. pp.933-5
Source: PubMed

ABSTRACT Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterized by dilatation and akinesis of the right ventricle, and causes life-threatening ventricular arrhythmia. Mutations of plakophilin-2 (PKP2) have recently been identified as one causative abnormality in ARVC. A case of ARVC with a mutation of PKP2 is reported here. Direct sequencing of the patient's DNA revealed an insertion mutation in exon 8 of PKP2 (1728_1729insGATG). The mutation caused the frameshift and the premature termination of translation (R577DfsX5). This is the first case report of PKP2 mutation found in Japanese ARVC patients.

0 0
 · 
0 Bookmarks
 · 
34 Views
  • Source
    Article: Mutations of plakophilin-2 in Chinese with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
    Xiaoliang Qiu, Wenling Liu, Dayi Hu, Tiangang Zhu, Cuilan Li, Lei Li, Chengjun Guo, Xingpeng Liu, Lei Wang, Hua Zheng, Chunling Wang, Qing Diao, Dan Shi, Pingyun Zhan, Yuanming Deng, Kunshen Liu, Yi Wang, Baomin Liu, Hongming Liu, Li Zhang
    [show abstract] [hide abstract]
    ABSTRACT: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart muscle disease associated with increased risks of sudden death, particularly in young, otherwise healthy, patients. The pathologic features are progressive myocardial atrophy and fibrofatty replacement. Plakophilin-2 (PKP2) is reported as the most common ARVD/C-causing gene in Western countries. In this study we aimed to determine the prevalence of PKP2 mutations in Chinese patients with ARVD/C and their phenotype characteristics. Genotype and phenotype were investigated in a cohort of 18 unrelated Chinese patients with a clinical diagnosis of ARVD/C. Direct sequencing of PKP2 led to the identification of 5 novel heterozygous mutations (R158K, Q211X, L419S, A793D, and N852fsX930) in 39% of patients (7 of 18) with ARVD/C. Among them, N852fsX930 was found in 3 unrelated young patients who presented with symptomatic ventricular tachyarrhythmia. Nevertheless, no significant difference could be detected between patients with ARVD/C with (n = 7) and without (n = 11) PKP2 mutations with regard to the phenotype characteristics and clinical outcomes. Decreased penetrance was prominent in family members. In conclusion, 5 novel PKP2 mutations were identified in a cohort of symptomatic Chinese patients with ARVD/C. N852fsX930 appeared to be a hot-spot mutation in which patients presented with a severe ARVD/C phenotype, and 2/3 had early onset of arrhythmic events. No significant difference was found in phenotype characteristics between patients with ARVD/C with and without PKP2 mutations. The decreased penetrance indicated that an ARVD/C diagnosis cannot solely rely on genotyping results.
    The American journal of cardiology 06/2009; 103(10):1439-44. · 3.58 Impact Factor
  • Source
    Article: Molecular cloning and developmental expression of plakophilin 2 in zebrafish.
    Miriam A Moriarty, Eva D Martin, Lucy Byrnes, Maura Grealy
    [show abstract] [hide abstract]
    ABSTRACT: Armadillo proteins are involved in providing strength and support to cells and tissues, nuclear transport, and transcriptional activation. In this report, we describe the identification and characterisation of the cDNA of the desmosomal armadillo protein plakophilin 2 in zebrafish. The 2448bp coding sequence encodes a predicted 815 amino acid protein, with nine armadillo repeats characteristic of the p120-catenin subfamily. It shares conserved N-glycosylation, myristoylation, and glycogen synthase kinase 3, casein kinase 2, and protein kinase C phosphorylation sites with mammalian armadillo proteins including plakoglobin and beta-catenin. Semi-quantitative reverse transcription polymerase chain reaction and whole mount in situ hybridisation show that it is expressed both maternally and zygotically. It is ubiquitously expressed during blastula stages but becomes restricted to epidermal and cardiac tissue during gastrulation. These results provide evidence that zebrafish plakophilin 2 is developmentally regulated with potential roles in cell adhesion, signalling, and cardiac and skin development.
    Biochemical and Biophysical Research Communications 03/2008; 367(1):124-9. · 2.48 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

ARVC
 
causative abnormality
 
causes life-threatening ventricular arrhythmia
 
Direct sequencing
 
exon 8
 
first case report
 
insertion mutation
 
Japanese ARVC patients
 
mutation
 
Mutations
 
patient's DNA
 
PKP2 mutation
 
premature termination