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Clinical and genetic characterization of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy caused by a plakophilin-2 splice mutation.
- Source :
-
Cardiology [Cardiology] 2012; Vol. 123 (3), pp. 181-9. Date of Electronic Publication: 2012 Nov 07. - Publication Year :
- 2012
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Abstract
- Objectives: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by fibrofatty replacement of cardiomyocytes. In around 50% of index patients, a genetic predisposition is demonstrated. The purpose of this study was to examine a plakophilin-2 (PKP2) splice site mutation, c.2489+4A>C, identified in 4 separately ascertained Dutch ARVD/C families.<br />Methods: Genealogical studies and comprehensive screening of 5 desmosomal genes were undertaken. Reverse transcriptase PCR (RT-PCR) and subsequent sequencing was performed.<br />Results: An A-to-C change (c.2489+4A>C) near the splice donor site of intervening sequence 12 of PKP2 was found in all 4 families. Based on pedigree data and haplotype sharing, a common ancestor should be situated more than 7 generations ago. RT-PCR demonstrated the presence of aberrant messenger RNA. Clinical manifestations ranged from severe disease to nonpenetrance in elderly mutation carriers.<br />Conclusions: This founder mutation in PKP2 is predicted to lead to the presence of a dysfunctional PKP2 protein, whereas most truncating mutations are expected to lead to loss of protein. Mutation carriers displayed a wide range of disease severity, suggesting that PKP2 mutations alone are not sufficient to cause disease, which results in the variable expression and incomplete penetrance characteristic of ARVD/C mutations.<br /> (Copyright © 2012 S. Karger AG, Basel.)
Details
- Language :
- English
- ISSN :
- 1421-9751
- Volume :
- 123
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 23147395
- Full Text :
- https://doi.org/10.1159/000342717