{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:53:58Z","timestamp":1768586038400,"version":"3.49.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hypokalemic periodic paralysis (HypoKPP) is a rare neuromuscular genetic disorder causing recurrent episodes of flaccid paralysis. Most cases are associated with <jats:italic>CACNA1S<\/jats:italic> mutation, causing defect of calcium channel and subsequent impairment of muscle functions. Due to defined management approaches early diagnosis is crucial for promptly treatment and prevention new attacks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We report a case of HypoKPP associated with previously unreported mutation in <jats:italic>CACNA1S<\/jats:italic> gene (p.R900M). Molecular modeling of Ca<jats:sub>V<\/jats:sub>1.1 was applied to evaluate its pathogenicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As a patient referred between attacks neurological status, laboratory and neurophysiological examination were unremarkable. Molecular modeling predicted that the p.R900M mutation affects the process of calcium channels activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Novel <jats:italic>CACNA1S<\/jats:italic> mutation, associated with HypoKPP was identified. Monte-Carlo energy minimization of the Ca<jats:sub>V<\/jats:sub>1.1 model supported the association of this mutation with this disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1267426","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T13:45:10Z","timestamp":1695995110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case report: A novel CACNA1S mutation associated with hypokalemic periodic paralysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Evgenii P.","family":"Nuzhnyi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina S.","family":"Arestova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey V.","family":"Rossokhin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna O.","family":"Protopopova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataliya Yu","family":"Abramycheva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia A.","family":"Suponeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey N.","family":"Illarioshkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/mus.26009","article-title":"Review of the diagnosis and treatment of periodic paralysis","volume":"57","author":"Statland","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1093\/brain\/awh639","article-title":"The primary periodic paralyses: diagnosis, pathogenesis and treatment","volume":"129","author":"Venance","year":"2006","journal-title":"Brain"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"OC17","DOI":"10.7860\/JCDR\/2015\/13237.6529","article-title":"Hypokalaemic periodic paralysis- a prospective study of the underlying etiologies","volume":"9","author":"Jandhyala","year":"2015","journal-title":"J Clin Diagn Res"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1212\/01.wnl.0000342387.65477.46","article-title":"Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis","volume":"72","author":"Matthews","year":"2009","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e202112946","DOI":"10.1085\/jgp.202112946","article-title":"Gating pore currents occur in Cav1.1 domain iii mutants associated with HypoPP","volume":"153","author":"Wu","year":"2021","journal-title":"J Gen Physiol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/nature05598","article-title":"Gating pore current in an inherited ion Channelopathy","volume":"446","author":"Sokolov","year":"2007","journal-title":"Nature"},{"key":"ref7","volume-title":"Electromyography and neuromuscular disorders: clinical-electrophysiologic correlations","author":"Preston","year":"2012"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.nmd.2015.09.006","article-title":"The R900S mutation in CACNA1S associated with hypokalemic periodic paralysis","volume":"25","author":"Ke","year":"2015","journal-title":"Neuromusc Disorde"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jns.2011.07.046","article-title":"A novel mutation in the calcium channel gene in a family with hypokalemic periodic paralysis","volume":"309","author":"Hirano","year":"2011","journal-title":"J Neurol Sci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/nature19321","article-title":"Structure of the voltage-gated calcium channel ca(V)1.1 at 3.6 a resolution","volume":"537","author":"Wu","year":"2016","journal-title":"Nature"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"6611","DOI":"10.1073\/pnas.84.19.6611","article-title":"Monte Carlo-minimization approach to the multiple-minima problem in protein folding","volume":"84","author":"Li","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1021\/ja00315a051","article-title":"A new force field for molecular mechanical simulation of nucleic acids and proteins","volume":"106","author":"Weiner","year":"1984","journal-title":"J Am Chem Soc"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10822-009-9317-9","article-title":"Docking flexible ligands in proteins with a solvent exposure- and distance-dependent dielectric function","volume":"24","author":"Garden","year":"2010","journal-title":"J Comput Aided Mol Des"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1124\/mol.110.068031","article-title":"Why does the inner-helix mutation A413C double the stoichiometry of Kv1.3 channel block by emopamil but not by verapamil?","volume":"79","author":"Rossokhin","year":"2011","journal-title":"Mol Pharmacol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"107795","DOI":"10.1016\/j.neuropharm.2019.107795","article-title":"The mechanisms of potentiation and inhibition of Gabaa receptors by non-steroidal anti-inflammatory drugs, mefenamic and niflumic acids","volume":"160","author":"Rossokhin","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nchembio.2353","article-title":"The chemical basis for electrical signaling","volume":"13","author":"Catterall","year":"2017","journal-title":"Nat Chem Biol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1146\/annurev-pharmtox-010818-021757","article-title":"Structure and pharmacology of voltage-gated sodium and calcium channels","volume":"60","author":"Catterall","year":"2020","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"E93","DOI":"10.1073\/pnas.1118434109","article-title":"Structural basis for gating charge movement in the voltage sensor of a sodium channel","volume":"109","author":"Yarov-Yarovoy","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.7554\/eLife.64087","article-title":"Structural determinants of voltage-gating properties in calcium channels","volume":"10","author":"Fernandez-Quintero","year":"2021","journal-title":"eLife"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1093\/hmg\/3.8.1415","article-title":"A calcium channel mutation causing hypokalemic periodic paralysis","volume":"3","author":"Jurkat-Rott","year":"1994","journal-title":"Hum Mol Genet"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1146\/annurev.ph.54.030192.000545","article-title":"Charge movement and the nature of signal transduction in skeletal muscle excitation-contraction coupling","volume":"54","author":"Rios","year":"1992","journal-title":"Annu Rev Physiol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e202112915","DOI":"10.1085\/jgp.202112915","article-title":"The distinct role of the four voltage sensors of the skeletal Cav1.1 channel in voltage-dependent activation","volume":"153","author":"Savalli","year":"2021","journal-title":"J Gen Physiol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.neuron.2005.06.012","article-title":"Ion permeation through a voltage- sensitive gating pore in brain sodium channels having voltage sensor mutations","volume":"47","author":"Sokolov","year":"2005","journal-title":"Neuron"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1085\/jgp.117.5.469","article-title":"Histidine scanning mutagenesis of basic residues of the S4 segment of the shaker K+ channel","volume":"117","author":"Starace","year":"2001","journal-title":"J Gen Physiol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1085\/jgp.200709755","article-title":"A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore","volume":"130","author":"Struyk","year":"2007","journal-title":"J Gen Physiol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.clinph.2019.12.414","article-title":"In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis","volume":"131","author":"Tan","year":"2020","journal-title":"Clin Neurophysiol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1007\/s12031-011-9596-1","article-title":"A novel mutation in CACNA1S gene associated with hypokalemic periodic paralysis which has a gender difference in the penetrance","volume":"46","author":"Li","year":"2012","journal-title":"J Mol Neurosci"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s00424-020-02368-3","article-title":"Skeletal muscle CaV1.1 channelopathies","volume":"472","author":"Flucher","year":"2020","journal-title":"Pflugers Arch"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e18873","DOI":"10.7759\/cureus.18873","article-title":"Vacuolar myopathy associated to CACNA1S mutation as a rare cause of late-onset limb-girdle myopathy: a Case report","volume":"13","author":"L\u00f3pez-Hern\u00e1ndez","year":"2021","journal-title":"Cureus"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"17560","DOI":"10.1038\/s41598-019-54041-0","article-title":"Myotonia in a patient with a mutation in an S4 arginine residue associated with hypokalaemic periodic paralysis and a concomitant synonymous CLCN1 mutation","volume":"9","author":"Thor","year":"2019","journal-title":"Sci Rep"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1267426\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T13:45:13Z","timestamp":1695995113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1267426\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,29]]},"references-count":31,"alternative-id":["10.3389\/fneur.2023.1267426"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1267426","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,29]]},"article-number":"1267426"}}