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Article

The Desmin (DES) Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy

1
National Medical Research Center for Therapy and Preventive Medicine, Petroverigsky per., 10, bld. 3, 101000 Moscow, Russia
2
Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany
3
Kurchatov Genomics Center-ARRIAB, All-Russia Research Institute of Agricultural Biotechnology, Timiryazevskaya Street, 42, 127550 Moscow, Russia
4
Medical Research and Educational Center, Lomonosov Moscow State University, Lomonosovsky Prospect 27, Building 10, 119991 Moscow, Russia
5
National Medical Research Center for Cardiology, 3-ya Cherepkovskaya Street, 15A, 121552 Moscow, Russia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2021, 12(1), 121; https://doi.org/10.3390/genes12010121
Received: 14 December 2020 / Revised: 4 January 2021 / Accepted: 15 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue Cardiovascular Genetics)
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. View Full-Text
Keywords: cardiomyopathy; desmin; DES; desminopathy; desmoplakin; DSP; left-ventricular non-compaction cardiomyopathy; cardiovascular genetics; dilated cardiomyopathy cardiomyopathy; desmin; DES; desminopathy; desmoplakin; DSP; left-ventricular non-compaction cardiomyopathy; cardiovascular genetics; dilated cardiomyopathy
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MDPI and ACS Style

Kulikova, O.; Brodehl, A.; Kiseleva, A.; Myasnikov, R.; Meshkov, A.; Stanasiuk, C.; Gärtner, A.; Divashuk, M.; Sotnikova, E.; Koretskiy, S.; Kharlap, M.; Kozlova, V.; Mershina, E.; Pilus, P.; Sinitsyn, V.; Milting, H.; Boytsov, S.; Drapkina, O. The Desmin (DES) Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy. Genes 2021, 12, 121. https://doi.org/10.3390/genes12010121

AMA Style

Kulikova O, Brodehl A, Kiseleva A, Myasnikov R, Meshkov A, Stanasiuk C, Gärtner A, Divashuk M, Sotnikova E, Koretskiy S, Kharlap M, Kozlova V, Mershina E, Pilus P, Sinitsyn V, Milting H, Boytsov S, Drapkina O. The Desmin (DES) Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy. Genes. 2021; 12(1):121. https://doi.org/10.3390/genes12010121

Chicago/Turabian Style

Kulikova, Olga, Andreas Brodehl, Anna Kiseleva, Roman Myasnikov, Alexey Meshkov, Caroline Stanasiuk, Anna Gärtner, Mikhail Divashuk, Evgeniia Sotnikova, Sergey Koretskiy, Maria Kharlap, Viktoria Kozlova, Elena Mershina, Polina Pilus, Valentin Sinitsyn, Hendrik Milting, Sergey Boytsov, and Oxana Drapkina. 2021. "The Desmin (DES) Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy" Genes 12, no. 1: 121. https://doi.org/10.3390/genes12010121

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