Sequenom MassARRAY approach in the arrhythmogenic right ventricular cardiomyopathy post-mortem setting: clinical and
M Alcalde1, O Campuzano, C Allegue
1Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain.
International Journal of Legal Medicine
|May 17, 2014
Summary
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is linked to desmosome mutations. Genetic testing in post-mortem samples identified pathogenic variants, with plakoglobin reduction observed in PKP2 mutation carriers.
Area of Science:
- Cardiovascular Pathology
- Molecular Cardiology
- Genetic Medicine
Background:
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited heart disease.
- It involves fibrofatty replacement of the myocardium, increasing sudden cardiac death risk.
- Reduced plakoglobin (PKG) at intercalated disks is a known ARVC hallmark.
Purpose of the Study:
- To investigate the role of desmosome gene mutations in ARVC's histological features.
- To correlate genetic findings with protein expression in ARVC heart tissues.
Main Methods:
- Genetic analysis of 48 ARVC cases (42 post-mortem, 6 living patients).
- Sequenom MassARRAY and Sanger sequencing for mutation detection.
- Immunohistochemical analysis of desmosomal proteins and Connexin 43 in post-mortem tissues.
Main Results:
- Identified three pathogenic mutations (PKP2, DSC2) in 7.14% of post-mortem ARVC samples.
- PKP2 mutation carriers showed absent or reduced plakoglobin (PKG) at intercalated disks.
- DSC2 mutation carriers had normal PKG levels; Connexin 43 remained unchanged in all ARVC samples.
Conclusions:
- Sequenom MassARRAY is effective for post-mortem ARVC genetic diagnosis.
- Plakoglobin reduction at intercalated disks is associated with specific desmosome gene mutations (PKP2).
- Desmosome protein alterations, excluding PKG, and Cx43 appear unaffected in this ARVC cohort.
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