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

Figures

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  Fig. 1. Amino acid position Y145 of the Kir2.1 channel is highly conserved in mammals. a Schematic representation of the localization of variant Y145C in a Kir2.1 channel subunit. The detected mutation (indicated by the red dot) results in an amino acid substitution in the pore forming region (H5). b Alignment of the Kir2.1 channel amino acid sequence among mammals. The alignment displays a partial sequence in human (Homo sapiens), mouse (Mus musculus), dog (Canis lupus familiaris), pig (Sus scrofa) and cattle (Bos taurus)

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  Fig. 2. The mutant p.Y145C was detected in a family with diagnosed ATS. a Pedigree of the family. Filled symbols indicate clinically affected individuals. +/− represents heterozygous carriers of mutation Y145C in KCNJ2 and −/− indicates exclusion of Y145C. Crossed symbols represent deceased family members. b ATS index patient (arrow in a) exhibiting typical clinical symptoms such as small chin, low-set ears and hypertelorism (not shown) c Prominent U-waves in resting ECG (scale 50 mm/s) of the ATS patient. Reprinted with permission from Beckmann and Kääb as well as the Hans Marseille Verlag [21]

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  Fig. 3. Representative currents and current/voltage relations recorded from HEK293 cells expressing different Kir2.1 constructs. a Current traces of HEK293 cells expressing WT Kir2.1 channels or the Y145C mutant alone. WT and mutant were also co-transfected in a 1/1 or 1/3 ratio (wt/mut). b Mean current/voltage relations (± standard deviation) from measurements as in a from HEK293 cells expressing WT (●), mutant (○) or a 1:1 (▲) or 1:3 mixture (△) of WT and mutant channels. The mean value of the WT current at −120 mV is significantly higher (p < 0.01, **) than any of the other constructs. At −120 mV, co-expression of WT and mutant generates an inward current, which is significantly higher (p < 0.05; *) than those measured with the mutant channel only

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  Fig. 4. Cellular localization of GFP tagged wild type and mutant Kir2.1 channels expressed in HEK293 cells. a EGFP fluorescence signal of a cell expressing Kir2.1 wild type. b EGFP fluorescence signal of a cell expressing Kir2.1 mutant p.Y145C. Both images were taken in the equatorial plane of cells using confocal laser scanning microscopy