A novel CACNA1S gene variant in a child with hypokalemic periodic paralysis: a case report and literature review

Figures

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  Fig. 1. Genetic studies of the family. (a) Whole-exome sequencing and confirmation by Sanger sequencing revealed that the proband was heterozygous for c.497 C > A (p.Ala166Asp) in the CACNA1S gene, which was inherited from his father. (b) The A166D variant occurs at a highly conserved position in CACNA1S of different species. (c) The predicted three-dimensional structure of the Cav1.1 protein denotes the effect of protein changes in A166D.

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  Fig. 2. Schematic of the Cav1.1 protein showing pathogenic variants associated with different phenotypes Shown are the locations of pathogenic or likely pathogenic variants of CACNA1S gene. Cav1.1 is composed of four repeated domains (DI–DIV), each containing six transmembrane segments (S1–S6), with S1–S4 representing the voltage-sensor domains and S5–S6 forming pore domains. Variants associated with HypoPP are indicated by red circles, whereas variants identified in individuals with malignant hyperthermia susceptibility are indicated by orange circles. The green circles denote missense variants identified in patients with congenital myopathy, whereas the green crosses represent truncated variants associated with congenital myopathy. The red pentagram indicates the variant in our patient

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  Fig. 3. Phenotype-genotype comparison by types of CACNA1S gene variants. Truncated variants are grouped in a unique category; missense variants are grouped by localization of the amino-acid substitution. HypoPP: hypokalemic periodic paralysis; MHS: malignant hyperthermia susceptibility; CM: congenital myopathy; TM: transmembrane