Scheiper, Stefanie ; Hertel, Brigitte ; Beckmann, Britt-Maria ; Kääb, Stefan ; Thiel, Gerhard ; Kauferstein, Silke (2017)
Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients.
In: BMC medical genetics, 18 (1)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
BACKGROUND
Mutations in the KCNJ2 gene encoding the ion channel Kir2.1 have been linked to the Andersen-Tawil syndrome (ATS). Molecular genetic screening performed in a family exhibiting clinical ATS phenotypes unmasked a novel sequence variant (c.434A > G, p.Y145C) in this gene. The aim of this study was to investigate the effect of this variant on Kir2.1 ion channel functionality.
METHODS
Mutant as well as wild type GFP tagged Kir2.1 channels were expressed in HEK293 cells. In order to examine the effect of the new variant, electrophysiological measurements were performed using patch clamp technique. Cellular localization of the mutant in comparison to the wild type ion channel was analyzed by confocal laser scanning microscopy.
RESULTS
The currents of cells expressing only mutant channels or a mixture of wild type and mutant were significantly reduced compared to those expressing wild type (WT) channels (p < 0.01). Whereas WT expressing cells exhibited at -120 mV an averaged current of -4.5 ± 1.9 nA, the mutant generates only a current of -0.17 ± 0.07 nA. A co-expression of mutant and WT channel generates only a partial rescue of the WT current. Confocal laser scanning microscopy indicated that the novel variant is not interfering with synthesis and/or protein trafficking.
CONCLUSIONS
The detected sequence variant causes loss-of-function of the Kir2.1 channel and explains the clinical phenotypes observed in Andersen-Tawil syndrome patients.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2017 |
| Autor(en): | Scheiper, Stefanie ; Hertel, Brigitte ; Beckmann, Britt-Maria ; Kääb, Stefan ; Thiel, Gerhard ; Kauferstein, Silke |
| Art des Eintrags: | Bibliographie |
| Titel: | Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients. |
| Sprache: | Englisch |
| Publikationsjahr: | 10 Oktober 2017 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | BMC medical genetics |
| Jahrgang/Volume einer Zeitschrift: | 18 |
| (Heft-)Nummer: | 1 |
| Kurzbeschreibung (Abstract): | BACKGROUND Mutations in the KCNJ2 gene encoding the ion channel Kir2.1 have been linked to the Andersen-Tawil syndrome (ATS). Molecular genetic screening performed in a family exhibiting clinical ATS phenotypes unmasked a novel sequence variant (c.434A > G, p.Y145C) in this gene. The aim of this study was to investigate the effect of this variant on Kir2.1 ion channel functionality. METHODS Mutant as well as wild type GFP tagged Kir2.1 channels were expressed in HEK293 cells. In order to examine the effect of the new variant, electrophysiological measurements were performed using patch clamp technique. Cellular localization of the mutant in comparison to the wild type ion channel was analyzed by confocal laser scanning microscopy. RESULTS The currents of cells expressing only mutant channels or a mixture of wild type and mutant were significantly reduced compared to those expressing wild type (WT) channels (p < 0.01). Whereas WT expressing cells exhibited at -120 mV an averaged current of -4.5 ± 1.9 nA, the mutant generates only a current of -0.17 ± 0.07 nA. A co-expression of mutant and WT channel generates only a partial rescue of the WT current. Confocal laser scanning microscopy indicated that the novel variant is not interfering with synthesis and/or protein trafficking. CONCLUSIONS The detected sequence variant causes loss-of-function of the Kir2.1 channel and explains the clinical phenotypes observed in Andersen-Tawil syndrome patients. |
| ID-Nummer: | pmid:29017447 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Plant Membrane Biophyscis (am 20.12.23 umbenannt in Biologie der Algen und Protozoen) |
| Hinterlegungsdatum: | 18 Okt 2017 07:12 |
| Letzte Änderung: | 18 Okt 2017 07:12 |
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