Case report: A novel CACNA1S mutation associated with hypokalemic periodic paralysis

Figures

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  Figure 1. (A) The pedigree chart. The arrow indicates the proband with HypoKPP (Wt—wild type allele). (B) Sanger sequencing chromatograms (revers variant) shows wild type allele (a) and c.2699G > T mutation (b).

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  Figure 2. Architecture of the hetero-tetrameric voltage-gated human calcium channel CaV1.1. (A) Schematic representation of four domains (I–IV) of the α1S subunit. S1–S6 transmembrane helices and four positive charges of S4 helix are shown in each domain. (B) Alignment of S4 segments of domains I-IV of CaV1.1. Positively charged Arg residues (R1-R4) are highlighted in color. The Arg900Met mutation is highlighted in the IIIS4M (mutated) segment. (C) Structural model of the α1S subunit of CaV1.1. View from the extracellular space is presented. The color coding of domains corresponds to (A). Transmembrane helices S1–S4 forming a voltage sensor (VS) are denoted in domain III. Yellow sphere in the center represents Ca2+ ion in the selective filter of the channel. (D,E) Structural models of VS-III in the activated state in the native and mutated forms, respectively. Residues R1-R4 of the S4 helix are shown, as well as residues E819, D836, E846, and F843 of the S2 helix interacting with them. The side chain of R900 is highlighted in yellow (D). Ionic contacts formed by R900 with residues E819 and D836 are shown as red dashed lines.