Te Rijdt, WP;
Asimaki, A;
Jongbloed, JDH;
Hoorntje, ET;
Lazzarini, E;
van der Zwaag, PA;
de Boer, RA;
van Tintelen, JP;
Saffitz, JE;
van den Berg, MP;
et al.
Te Rijdt, WP; Asimaki, A; Jongbloed, JDH; Hoorntje, ET; Lazzarini, E; van der Zwaag, PA; de Boer, RA; van Tintelen, JP; Saffitz, JE; van den Berg, MP; Suurmeijer, AJH
(2019)
Distinct molecular signature of phospholamban p.Arg14del arrhythmogenic cardiomyopathy.
Cardiovasc Pathol, 40.
pp. 2-6.
ISSN 1879-1336
https://doi.org/10.1016/j.carpath.2018.12.006
SGUL Authors: Asimaki, Angeliki
Abstract
Phospholamban (PLN) p.Arg14del cardiomyopathy is characterized by a distinct arrhythmogenic biventricular phenotype that can be predominantly left ventricular, right ventricular, or both. Our aim was to further elucidate distinct features of this cardiomyopathy with respect to the distribution of desmosomal proteins observed by immunofluorescence (IF) in comparison to desmosomal arrhythmogenic cardiomyopathy and co-existent genetic variants. We studied eight explanted heart specimens from PLN p.Arg14del mutation carriers. Macro- and microscopic examination revealed biventricular presence of fibrofatty replacement and interstitial fibrosis. Five out of 8 (63%) patients met consensus criteria for both arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy (DCM). In four cases, targeted next-generation sequencing revealed one additional pathogenic variant and six variants of unknown significance. IF showed diminished junction plakoglobin signal intensity at the intercalated disks in 4 (67%) out of 6 cases fulfilling ARVC criteria but normal intensity in both cases fulfilling only DCM criteria. Notably, the four cases with diminished junction plakoglobin were also those where an additional gene variant was detected. IF for two proteins recently investigated in desmosomal arrhythmogenic cardiomyopathy (ACM), synapse-associated protein 97 and glycogen synthase kinase-3 beta, showed a distinct distributional pattern in comparison to desmosomal ACM. In 7 (88%) out of 8 cases we observed both a strong synapse-associated protein 97 signal at the sarcomeres and no glycogen synthase kinase-3 beta translocation to the intercalated discs. Phospholamban p.Arg14del cardiomyopathy is characterized by a distinct molecular signature compared to desmosomal ACM, specifically a different desmosomal protein distribution. This study substantiates the idea that additional genetic variants play a role in the phenotypical heterogeneity.
Item Type: |
Article
|
Additional Information: |
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: |
Arrhythmogenic cardiomyopathy, Dilated cardiomyopathy, Immunofluorescence, Next-generation sequencing, Phospholamban, Arrhythmogenic cardiomyopathy, Dilated cardiomyopathy, Immunofluorescence, Next-generation sequencing, Phospholamban, 1102 Cardiovascular Medicine And Haematology, Cardiovascular System & Hematology |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Cardiovasc Pathol |
ISSN: |
1879-1336 |
Language: |
eng |
Dates: |
Date | Event |
---|
May 2019 | Published | 21 December 2018 | Published Online | 14 December 2018 | Accepted |
|
Publisher License: |
Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 |
PubMed ID: |
30763825 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/110681 |
Publisher's version: |
https://doi.org/10.1016/j.carpath.2018.12.006 |
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