A novel CACNA1S variant (p.Arg528Leu) is associated with rhabdomyolysis and hyperCKemia, expanding the phenotypic spectrum of Cav1.1 mutations to resemble RYR1 mutations.
Novel CACNA1S phenotype expands the mutational spectrum; leaves open causality and diagnostic implications pending validation.
Background and purpose CACNA 1S encodes Ca v 1.1, a voltage sensor for muscle excitation−contraction coupling, which activates the ryanodine receptor 1 ( RYR 1) leading to calcium release from the sarcoplasmic reticulum. CACNA 1S mutations cause hypokalemic periodic paralysis, malignant hyperthermia and congenital myopathy. RYR 1 mutations result in congenital myopathy, malignant hyperthermia and rhabdomyolysis. Methods The aim was to describe a novel phenotype associated with a CACNA 1S variant at a site previously linked to hypokalemic periodic paralysis. Results The patient presented with fluctuating asymptomatic creatine kinase elevation after an episode of rhabdomyolysis but has no history of periodic paralysis. His muscle biopsy showed core‐like structures occurring mainly in type 2 fibers. He carries a novel Ca v 1.1 variant (p.Arg528Leu) affecting a highly conserved amino acid. Different mutations at the same location cause hypokalemic periodic paralysis. Conclusion This case underscores the similarity between the phenotypes caused by mutations in two functionally linked proteins, RYR 1 and Ca v 1.1.
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Anandan et al. (2017) studied this question.
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