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BMC Medical Genetics

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Open Access 01-12-2017 | Research article

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

Authors: Stefanie Scheiper, Brigitte Hertel, Britt-Maria Beckmann, Stefan Kääb, Gerhard Thiel, Silke Kauferstein

Published in: BMC Medical Genetics | Issue 1/2017

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.

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Title: Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients
Authors: Stefanie Scheiper
Brigitte Hertel
Britt-Maria Beckmann
Stefan Kääb
Gerhard Thiel
Silke Kauferstein
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-017-0472-x

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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