scholarly journals The Double Mutation DSG2-p.S363X and TBX20-p.D278X Is Associated with Left Ventricular Non-Compaction Cardiomyopathy: Case Report

2021 ◽  
Vol 22 (13) ◽  
pp. 6775
Author(s):  
Roman Myasnikov ◽  
Andreas Brodehl ◽  
Alexey Meshkov ◽  
Olga Kulikova ◽  
Anna Kiseleva ◽  
...  

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disease, with or without left ventricular dysfunction, which is characterized by a two-layer structure of the myocardium and an increased number of trabeculae. The study of familial forms of LVNC is helpful for risk prediction and genetic counseling of relatives. Here, we present a family consisting of three members with LVNC. Using a next-generation sequencing approach a combination of two (likely) pathogenic nonsense mutations DSG2-p.S363X and TBX20-p.D278X was identified in all three patients. TBX20 encodes the cardiac T-box transcription factor 20. DSG2 encodes desmoglein–2, which is part of the cardiac desmosomes and belongs to the cadherin family. Since the identified nonsense variant (DSG2-p.S363X) is localized in the extracellular domain of DSG2, we performed in vitro cell transfection experiments. These experiments revealed the absence of truncated DSG2 at the plasma membrane, supporting the pathogenic relevance of DSG2-p.S363X. In conclusion, we suggest that in the future, these findings might be helpful for genetic screening and counseling of patients with LVNC.

2004 ◽  
Vol 43 (5) ◽  
pp. A22
Author(s):  
Lisa C Costello-Boerrigter ◽  
Guido Boerrigter ◽  
Gail J Harty ◽  
Alessandro Cataliotti ◽  
Denise M Heublein ◽  
...  

2016 ◽  
Vol 67 (13) ◽  
pp. 1354
Author(s):  
Nicola Maurea ◽  
Carmela Coppola ◽  
Giovanna Piscopo ◽  
Domenica Rea ◽  
Gennaro Riccio ◽  
...  

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 121
Author(s):  
Olga Kulikova ◽  
Andreas Brodehl ◽  
Anna Kiseleva ◽  
Roman Myasnikov ◽  
Alexey Meshkov ◽  
...  

Here, we present a small Russian family, where the index patient received a diagnosis of left-ventricular non-compaction cardiomyopathy (LVNC) in combination with a skeletal myopathy. Clinical follow-up analysis revealed a LVNC phenotype also in her son. Therefore, we applied a broad next-generation sequencing gene panel approach for the identification of the underlying mutation. Interestingly, DES-p.A337P was identified in the genomes of both patients, whereas only the index patient carried DSP-p.L1348X. DES encodes the muscle-specific intermediate filament protein desmin and DSP encodes desmoplakin, which is a cytolinker protein connecting desmosomes with the intermediate filaments. Because the majority of DES mutations cause severe filament assembly defects and because this mutation was found in both affected patients, we analyzed this DES mutation in vitro by cell transfection experiments in combination with confocal microscopy. Of note, desmin-p.A337P forms cytoplasmic aggregates in transfected SW-13 cells and in cardiomyocytes derived from induced pluripotent stem cells underlining its pathogenicity. In conclusion, we suggest including the DES gene in the genetic analysis for LVNC patients in the future, especially if clinical involvement of the skeletal muscle is present.


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