{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:23:53Z","timestamp":1790601833037,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T00:00:00Z","timestamp":1479945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Non-profit Hertie-Foundation"},{"name":"German Society for Muscle Disorders (DGM)"},{"name":"IonNeurOnet of the German Federal Ministry of Research (BMBF)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>Hyperkalemic periodic paralysis (<jats:styled-content style=\"fixed-case\">HyperPP<\/jats:styled-content>) is a dominantly inherited muscle disease caused by mutations in <jats:italic><jats:styled-content style=\"fixed-case\">SCN4A<\/jats:styled-content><\/jats:italic> gene encoding skeletal muscle voltage gated Na<jats:italic><jats:sub>v<\/jats:sub><\/jats:italic>1.4 channels. We identified a novel Na<jats:italic><jats:sub>v<\/jats:sub><\/jats:italic>1.4 mutation <jats:styled-content style=\"fixed-case\">I692M<\/jats:styled-content> in 14 families out of the 104 genetically identified <jats:styled-content style=\"fixed-case\">HyperPP<\/jats:styled-content> families in the Neuromuscular Centre Ulm and is therefore as frequent as <jats:styled-content style=\"fixed-case\">I693T<\/jats:styled-content> (13 families out of 14 <jats:styled-content style=\"fixed-case\">HyperPP<\/jats:styled-content> families) in Germany. Surprisingly, in 13 families, a known polymorphism <jats:styled-content style=\"fixed-case\">S906T<\/jats:styled-content> was also present. It was on the affected allele in at least 10 families compatible with a possible founder effect in central Europe. All affected members suffered from episodic weakness; myotonia was also common. Compared with <jats:styled-content style=\"fixed-case\">I692M<\/jats:styled-content> patients, <jats:styled-content style=\"fixed-case\">I692M\u2010S906T<\/jats:styled-content> patients had longer weakness episodes, more affected muscles, <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content> elevation and presence of permanent weakness. Electrophysiological investigation showed that both mutants had incomplete slow inactivation and a hyperpolarizing shift of activation which contribute to membrane depolarization and weakness. Additionally, <jats:styled-content style=\"fixed-case\">I692M\u2010S906T<\/jats:styled-content> significantly enhanced close\u2010state fast inactivation compared with <jats:styled-content style=\"fixed-case\">I692M<\/jats:styled-content> alone, suggesting a higher proportion of inactivated <jats:styled-content style=\"fixed-case\">I692M\u2010S906T<\/jats:styled-content> channels upon membrane depolarization which may facilitate the initiation of weakness episodes and therefore clinical manifestation. Our results suggest that polymorphism <jats:styled-content style=\"fixed-case\">S906T<\/jats:styled-content> has effects on the clinical phenotypic and electrophysiological severity of a novel borderline Na<jats:italic><jats:sub>v<\/jats:sub><\/jats:italic>1.4 mutation <jats:styled-content style=\"fixed-case\">I692M<\/jats:styled-content>, making the borderline mutation fully penetrant.<\/jats:p>","DOI":"10.1111\/cge.12880","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T02:41:55Z","timestamp":1476326515000},"page":"859-867","source":"Crossref","is-referenced-by-count":9,"title":["Effects of <scp>S906T<\/scp> polymorphism on the severity of a novel borderline mutation <scp>I692M<\/scp> in Na<i><sub>v<\/sub><\/i>1.4 cause periodic paralysis"],"prefix":"10.1111","volume":"91","author":[{"given":"C.","family":"Fan","sequence":"first","affiliation":[{"name":"Division of Neurophysiology Ulm University  Ulm 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