The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3

Brodehl A, Hain C, Flottmann F, Ratnavadivel S, Gaertner A, Klauke B, Kalinowski J, Korperich H, Gummert J, Paluszkiewicz L, Deutsch M-A, et al. (2021)
Biomedicines 9(10): 1400.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Brodehl, Andreas; Hain, CarstenUniBi; Flottmann, Franziska; Ratnavadivel, Sandra; Gaertner, Anna; Klauke, Barbel; Kalinowski, JörnUniBi; Korperich, Hermann; Gummert, Jan; Paluszkiewicz, Lech; Deutsch, Marcus-Andre; Milting, Hendrik
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Abstract / Bemerkung
Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation DES-c.735G>C. As DES-c.735G>C affects the last base pair of exon-3, it is unknown whether putative missense or splice site mutations are caused. Therefore, we applied nanopore amplicon sequencing revealing the expression of a transcript without exon-3 in the explanted myocardial tissue of the index patient. Western blot analysis verified this finding at the protein level. In addition, we performed cell culture experiments revealing an abnormal cytoplasmic aggregation of the truncated desmin form (p.D214-E245del) but not of the missense variant (p.E245D). In conclusion, we show that DES-c.735G>C causes a splicing defect leading to exon-3 skipping of the DES gene. DES-c.735G>C can be classified as a pathogenic mutation associated with RCM and atrial fibrillation. In the future, this finding might have relevance for the genetic understanding of similar cases.
Erscheinungsjahr
2021
Zeitschriftentitel
Biomedicines
Band
9
Ausgabe
10
Art.-Nr.
1400
eISSN
2227-9059
Page URI
https://pub.uni-bielefeld.de/record/2958745

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Brodehl A, Hain C, Flottmann F, et al. The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3. Biomedicines. 2021;9(10): 1400.
Brodehl, A., Hain, C., Flottmann, F., Ratnavadivel, S., Gaertner, A., Klauke, B., Kalinowski, J., et al. (2021). The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3. Biomedicines, 9(10), 1400. https://doi.org/10.3390/biomedicines9101400
Brodehl, A., Hain, C., Flottmann, F., Ratnavadivel, S., Gaertner, A., Klauke, B., Kalinowski, J., Korperich, H., Gummert, J., Paluszkiewicz, L., et al. (2021). The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3. Biomedicines 9:1400.
Brodehl, A., et al., 2021. The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3. Biomedicines, 9(10): 1400.
A. Brodehl, et al., “The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3”, Biomedicines, vol. 9, 2021, : 1400.
Brodehl, A., Hain, C., Flottmann, F., Ratnavadivel, S., Gaertner, A., Klauke, B., Kalinowski, J., Korperich, H., Gummert, J., Paluszkiewicz, L., Deutsch, M.-A., Milting, H.: The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3. Biomedicines. 9, : 1400 (2021).
Brodehl, Andreas, Hain, Carsten, Flottmann, Franziska, Ratnavadivel, Sandra, Gaertner, Anna, Klauke, Barbel, Kalinowski, Jörn, Korperich, Hermann, Gummert, Jan, Paluszkiewicz, Lech, Deutsch, Marcus-Andre, and Milting, Hendrik. “The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3”. Biomedicines 9.10 (2021): 1400.
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2021-11-25T14:54:52Z
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