Novel Mutation in Hypokalemic Periodic Paralysis: First Report with Functional Validation

G, S, Y, N (2021) Structural basis of the modulation of the Voltage-Gated calcium ion channel Ca v 1.1 by dihydropyridine Compounds*. Angew Chem Int Ed Engl 60(6):3131–3137. https://doi.org/10.1002/anie.202011793

Aburahma SK, Rousan LA, Shboul M, Biella F, Lucchiari S, Comi GP, Meola G, Pagliarani S (2024) Case report: dihydropyridine receptor (CACNA1S) congenital myopathy, a novel phenotype with early onset periodic paralysis. Front Neurol 15:1359479. https://doi.org/10.3389/fneur.2024.1359479

Article  PubMed  PubMed Central  Google Scholar 

Beam TA, Loudermilk EF, Kisor DF (2017) Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia. Physiol Genomics 49(2):81–87. https://doi.org/10.1152/physiolgenomics.00126.2016

Article  CAS  PubMed  Google Scholar 

Blanton R, Afzal S (2022) Hypokalemic periodic paralysis exacerbated by carbohydrate load: A case report. Cureus 14(9):e28851. https://doi.org/10.7759/cureus.28851

Article  PubMed  PubMed Central  Google Scholar 

Brugnoni R, Canioni E, Filosto M, Pini A, Tonin P, Rossi T, Canavese C, Eoli M, Siciliano G, Lauria G, Mantegazza R, Maggi L (2022) Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes. Neurogenetics 23(1):19–25. https://doi.org/10.1007/s10048-021-00673-2

Article  CAS  PubMed  Google Scholar 

Callanan N, Wright N (2022) Single-centre case-control study investigating the association between acanthosis nigricans, insulin resistance and type 2 diabetes in a young, overweight, UK population. BMJ Paediatr Open 6(1). https://doi.org/10.1136/bmjpo-2022-001574

Dankar R, Barakat S, El-Charabaty E, Hashmi SSH, Sayegh E, S. E (2025) Unraveling an uncommon encounter: hypokalemic periodic paralysis with Brugada phenocopy amidst hypokalemia. Eur J Case Rep Intern Med 12(3):005195. https://doi.org/10.12890/2025_005195

Article  PubMed  PubMed Central  Google Scholar 

DiFranco M, Cannon SC (2022) Voltage-dependent Ca(2+) release is impaired in hypokalemic periodic paralysis caused by Ca(V)1.1-R528H but not by Na(V)1.4-R669H. Am J Physiol Cell Physiol 323(2):C478–c485. https://doi.org/10.1152/ajpcell.00209.2022

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fatima G, Dzupina A, Magomedova HBA, Siddiqui A, Mehdi Z, A., Hadi N (2024) Magnesium matters: A comprehensive review of its vital role in health and diseases. Cureus 16(10):e71392. https://doi.org/10.7759/cureus.71392

Article  PubMed  PubMed Central  Google Scholar 

Fiszer D, Shaw MA, Fisher NA, Carr IM, Gupta PK, Watkins EJ, de Sa R, Kim D, J. H., Hopkins PM (2015) Next-generation sequencing of RYR1 and CACNA1S in malignant hyperthermia and exertional heat illness. Anesthesiology 122(5):1033–1046. https://doi.org/10.1097/aln.0000000000000610

Article  CAS  PubMed  Google Scholar 

Gadiparthi S, Kalyanshettar S, Patil M, Patil SV (2024) Role of serum magnesium on insulin resistance in overweight and obese children. Cureus 16(9):e69622. https://doi.org/10.7759/cureus.69622

Article  PubMed  PubMed Central  Google Scholar 

Hannouneh ZA, Cervantes CE, Sperati CJ, Hanouneh M (2024) Familial hypokalemic periodic paralysis: a case induced by concurrent hyperthyroidism. BMC Nephrol 25(1):315. https://doi.org/10.1186/s12882-024-03749-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiao Y, Li W, Wang L, Jiang H, Wang S, Jia X, Wang Z, Wang H, Zhang B, Ding G (2022) Relationship between dietary magnesium intake and metabolic syndrome. Nutrients 14(10). https://doi.org/10.3390/nu14102013

Kubota T, Wu F, Vicart S, Nakaza M, Sternberg D, Watanabe D, Furuta M, Kokunai Y, Abe T, Kokubun N, Fontaine B, Cannon SC, Takahashi MP (2020) Hypokalaemic periodic paralysis with a charge-retaining substitution in the voltage sensor. Brain Commun 2(2):fcaa103. https://doi.org/10.1093/braincomms/fcaa103

Article  PubMed  PubMed Central  Google Scholar 

Kubota T, Takahashi S, Yamamoto R, Sato R, Miyanooto A, Yamamoto R, Yamauchi K, Homma K, Takahashi MP (2023) Optical measurement of gating pore currents in hypokalemic periodic paralysis model cells. Dis Model Mech 16(6). https://doi.org/10.1242/dmm.049704

Kumar S, Offiong EE, Sangita S, Hussain N (2018) Phenotypical variation with same genetic mutation in Familial hypokalemic periodic paralysis. J Pediatr Neurosci 13(2):218–220. https://doi.org/10.4103/jpn.JPN_44_17

Article  PubMed  PubMed Central  Google Scholar 

Kuo CC, Wu VC, Tsai CW, Huang KH, Wang SM, Li BC, Chang CC, Lu CC, Yang WS, Chao CT, Tsai IC, Lai CF, Lin WC, Wu MS, Lin YH, Lin CY, Chang HW, Wang WJ, Chiang WC, Wu KD (2011) Combining body mass index and serum potassium to urine potassium clearance ratio is an alternative method to predict primary aldosteronism. Clin Chim Acta 412(17–18):1637–1642. https://doi.org/10.1016/j.cca.2011.05.018

Article  CAS  PubMed  Google Scholar 

Kurokawa M, Torio M, Ohkubo K, Tocan V, Ohyama N, Toda N, Ishii K, Nishiyama K, Mushimoto Y, Sakamoto R, Nakaza M, Horie R, Kubota T, Takahashi MP, Sakai Y, Nomura M, Ohga S (2020) The expanding phenotype of hypokalemic periodic paralysis in a Japanese family with p. Val876Glu mutation in CACNA1S. Mol Genet Genomic Med 8(4):e1175. https://doi.org/10.1002/mgg3.1175

Article  PubMed  PubMed Central  Google Scholar 

Latorre R, Purroy F (2020) [Hypokalemic periodic paralysis: a systematic review of published case reports]. Rev Neurol 71(9):317–325. https://doi.org/10.33588/rn.7109.2020377(Parálisis periódica hipocaliémica: revisión sistemática de casos publicados.)

Article  CAS  PubMed  Google Scholar 

Palmer BF, Clegg DJ (2022) Extrarenal Effects of Aldosterone on Potassium Homeostasis. Kidney360(3):561–568 https://doi.org/10.34067/kid.0006762021

Park YM, Kwock CK, Park S, Eicher-Miller HA, Yang YJ (2018) An association of urinary sodium-potassium ratio with insulin resistance among Korean adults. Nutr Res Pract 12(5):443–448. https://doi.org/10.4162/nrp.2018.12.5.443

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pauzi MHM, Kadir AA, Dinsuhaimi SI, Yudin ZM, Yusuf WNW (2025) Quetiapine-induced hypokalemic periodic paralysis in a pregnant woman: a case report. Korean J Fam Med 46(2):115–119. https://doi.org/10.4082/kjfm.24.0301

Article  PubMed  PubMed Central  Google Scholar 

Pelizzari S, Heiss MC, Fernández-Quintero ML, Ghaleb E, Liedl Y, Tuluc KR, Campiglio P, M., Flucher BE (2024) Ca(V)1.1 voltage-sensing domain III exclusively controls skeletal muscle excitation-contraction coupling. Nat Commun 15(1):7440. https://doi.org/10.1038/s41467-024-51809-5

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qing G, Zakaria WNA, Rom FZM, Nik W, Zulkeflee HA, Rahim SN A (2025) Thyrotoxic hypokalemic periodic paralysis: pathophysiological mechanisms. Endocrinol Metab (Seoul). https://doi.org/10.3803/EnM.2025.2554

Article  PubMed  Google Scholar 

Reid DG, MacLachlan LK, Salter CJ, Saunders MJ, Jane SD, Lee AG, Tremeer EJ, Salisbury SA (1992) An electrophysiological and spectroscopic study of the properties and structure of biological calcium channels. Investigations of a model ion channel. Biochim Biophys Acta 1106(2):264–272. https://doi.org/10.1016/0005-2736(92)90005-7

Article  CAS  PubMed  Google Scholar 

Savalli N, Angelini M, Steccanella F, Wier J, Wu F, Quinonez M, DiFranco M, Neely A, Cannon SC, Olcese R (2021) The distinct role of the four voltage sensors of the skeletal CaV1.1 channel in voltage-dependent activation. J Gen Physiol 153(11). https://doi.org/10.1085/jgp.202112915

Statland JM, Fontaine B, Hanna MG, Johnson NE, Kissel JT, Sansone VA, Shieh PB, Tawil RN, Trivedi J, Cannon SC, Griggs RC (2018) Review of the diagnosis and treatment of periodic paralysis. Muscle Nerve 57(4):522–530. https://doi.org/10.1002/mus.26009

Article  CAS  PubMed  Google Scholar 

Tal B, Sack J, Yaron M, Shefer G, Buch A, Ben Haim L, Marcus Y, Shenkerman G, Sofer Y, Shefer L, Margaliot M, Stern N (2019) Increment in dietary potassium predicts weight loss in the treatment of the metabolic syndrome. Nutrients 11(6). https://doi.org/10.3390/nu11061256

Wu F, Mi W, Hernández-Ochoa EO, Burns DK, Fu Y, Gray HF, Struyk AF, Schneider MF, Cannon SC (2012) A calcium channel mutant mouse model of hypokalemic periodic paralysis. J Clin Invest 122(12):4580–4591. https://doi.org/10.1172/jci66091

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu J, Wang P, Li Y, Li G, Kaczmarek LK, Wu Y, Koni PA, Flavell RA, Desir GV (2004) The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity. Proc Natl Acad Sci U S A 101(9):3112–3117. https://doi.org/10.1073/pnas.0308450100

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yuan JH, Higuchi Y, Hashiguchi A, Ando M, Yoshimura A, Nakamura T, Hiramatsu Y, Sakiyama Y, Takashima H (2023) Gene panel analysis of 119 index patients with suspected periodic paralysis in Japan. Front Neurol 14:1078195. https://doi.org/10.3389/fneur.2023.1078195

Article  PubMed  PubMed Central  Google Scholar 

Zhao X, Ning H, Liu L, Zhu C

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