C Anandan1, M A Cipriani2, R S Laughlin1, Z Niu3,4, M Milone1. 1. Department of Neurology, Mayo Clinic, Rochester, MN, USA. 2. Department of Family Medicine, Mayo Clinic, Rochester, MN, USA. 3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 4. Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Abstract
BACKGROUND AND PURPOSE: CACNA1S encodes Cav 1.1, a voltage sensor for muscle excitation-contraction coupling, which activates the ryanodine receptor 1 (RYR1) leading to calcium release from the sarcoplasmic reticulum. CACNA1S mutations cause hypokalemic periodic paralysis, malignant hyperthermia and congenital myopathy. RYR1 mutations result in congenital myopathy, malignant hyperthermia and rhabdomyolysis. METHODS: The aim was to describe a novel phenotype associated with a CACNA1S 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 Cav 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, RYR1 and Cav 1.1.
BACKGROUND AND PURPOSE:CACNA1S encodes Cav 1.1, a voltage sensor for muscle excitation-contraction coupling, which activates the ryanodine receptor 1 (RYR1) leading to calcium release from the sarcoplasmic reticulum. CACNA1S mutations cause hypokalemic periodic paralysis, malignant hyperthermia and congenital myopathy. RYR1 mutations result in congenital myopathy, malignant hyperthermia and rhabdomyolysis. METHODS: The aim was to describe a novel phenotype associated with a CACNA1S 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 Cav 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, RYR1 and Cav 1.1.
Authors: Katrin Sangkuhl; Robert T Dirksen; Maria L Alvarellos; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2020-02 Impact factor: 2.000
Authors: Nyamkhishig Sambuughin; Ognoon Mungunsukh; Mingqiang Ren; John F Capacchione; Iren Horkayne-Szakaly; Kevin Chuang; Sheila M Muldoon; Jonathan K Smith; Francis G O'Connor; Patricia A Deuster Journal: Mol Genet Metab Rep Date: 2018-08-01