TY  - JOUR
A1  - Scheiper, Stefanie
A1  - Hertel, Brigitte
A1  - Beckmann, Britt-Maria
A1  - Kääb, Stefan
A1  - Thiel, Gerhard
A1  - Kauferstein, Silke
T1  - Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients
T2  - BMC medical genetics
N2  - 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.
KW  - Andersen-Tawil syndrome
KW  - KCNJ2 mutation
KW  - Potassium channel Kir2.1
KW  - Functional characterization
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43928
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-439289
SN  - 1471-2350
N1  - © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 18
IS  - 1, Art. 113
SP  - 1
EP  - 8
PB  - BioMed Central ; Springer
CY  - London ; Berlin ; Heidelberg
ER  -