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Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients.

Scheiper, Stefanie and Hertel, Brigitte and Beckmann, Britt-Maria and Kääb, Stefan and Thiel, Gerhard and Kauferstein, Silke (2017):
Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients.
In: BMC medical genetics, 18 (1), p. 113, ISSN 1471-2350,
[Article]

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.

Item Type: Article
Erschienen: 2017
Creators: Scheiper, Stefanie and Hertel, Brigitte and Beckmann, Britt-Maria and Kääb, Stefan and Thiel, Gerhard and Kauferstein, Silke
Title: Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients.
Language: English
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.

Journal or Publication Title: BMC medical genetics
Volume: 18
Number: 1
Divisions: 10 Department of Biology
10 Department of Biology > Plant Membrane Biophysics
Date Deposited: 18 Oct 2017 07:12
Identification Number: pmid:29017447
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