In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations

Gaertner A, Klauke B, Stork I, Niehaus K, Niemann G (2012)
PloS one 7(10): e47097.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
BACKGROUND: Although numerous sequence variants in desmoglein-2 (DSG2) have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the functional impact of new sequence variations is difficult to estimate. METHODOLOGY/PRINCIPAL FINDINGS: To test the functional consequences of DSG2-variants, we established an expression system for the extracellular domain and the full-length DSG2 using the human cell line HT1080. We established new tools to investigate ARVC-associated DSG2 variations and compared wild-type proteins and proteins with one of the five selected variations (DSG2-p.R46Q, -p.D154E, -p.D187G, -p.K294E, -p.V392I) with respect to prodomain cleavage, adhesion properties and cellular localisation. CONCLUSIONS/SIGNIFICANCE: The ARVC-associated DSG2-p.R46Q variation was predicted to be probably damaging by bioinformatics tools and to concern a conserved proprotein convertase cleavage site. In this study an impaired prodomain cleavage and an influence on the DSG2-properties could be demonstrated for the R46Q-variant leading to the classification of the variant as a potential gain-of-function mutant. In contrast, the variants DSG2-p.K294E and -p.V392I, which have an arguable impact on ARVC pathogenesis and are predicted to be benign, did not show functional differences to the wild-type protein in our study. Notably, the variants DSG2-p.D154E and -p.D187G, which were predicted to be damaging by bioinformatics tools, had no detectable effects on the DSG2 protein properties in our study.
PloS one


Gaertner A, Klauke B, Stork I, Niehaus K, Niemann G. In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations. PloS one. 2012;7(10):e47097.
Gaertner, A., Klauke, B., Stork, I., Niehaus, K., & Niemann, G. (2012). In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations. PloS one, 7(10), e47097. doi:10.1371/journal.pone.0047097
Gaertner, A., Klauke, B., Stork, I., Niehaus, K., and Niemann, G. (2012). In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations. PloS one 7, e47097.
Gaertner, A., et al., 2012. In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations. PloS one, 7(10), p e47097.
A. Gaertner, et al., “In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations”, PloS one, vol. 7, 2012, pp. e47097.
Gaertner, A., Klauke, B., Stork, I., Niehaus, K., Niemann, G.: In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations. PloS one. 7, e47097 (2012).
Gaertner, Anna, Klauke, Baerbel, Stork, Ines, Niehaus, Karsten, and Niemann, Gesa. “In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations”. PloS one 7.10 (2012): e47097.

8 Zitationen in Europe PMC

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