Sodium Channel Myotonia Due to Novel Mutations in Domain I of Nav1.4

Serena Pagliarani, Sabrina Lucchiari, Marina Scarlato, Elisa Redaelli, Anna Modoni, Francesca Magri, Barbara Fossati, Stefano C. Previtali, Valeria A. Sansone, Marzia Lecchi, Mauro Lo Monaco, Giovanni Meola, Giacomo P. Comi

Research output: Contribution to journalArticle

Abstract

Sodium channel myotonia is a form of muscle channelopathy due to mutations that affect the Nav1.4 channel. We describe seven families with a series of symptoms ranging from asymptomatic to clearly myotonic signs that have in common two novel mutations, p.Ile215Thr and p.Gly241Val, in the first domain of the Nav1.4 channel. The families described have been clinically and genetically evaluated. p.Ile215Thr and p.Gly241Val lie, respectively, on extracellular and intracellular loops of the first domain of the Nav1.4 channel. We assessed that the p.Ile215Thr mutation can be related to a founder effect in people from Southern Italy. Electrophysiological evaluation of the channel function showed that the voltage dependence of the activation for both the mutant channels was significantly shifted toward hyperpolarized potentials (Ile215Thr: −28.6 ± 1.5 mV and Gly241Val: −30.2 ± 1.3 mV vs. WT: −18.5 ± 1.3 mV). The slow inactivation was also significantly affected, whereas fast inactivation showed a different behavior in the two mutants. We characterized two novel mutations of the SCN4A gene expanding the knowledge about genetics of mild forms of myotonia, and we present, to our knowledge, the first homozygous patient with sodium channel myotonia.

Original languageEnglish
Article number255
JournalFrontiers in Neurology
Volume11
DOIs
Publication statusPublished - Apr 29 2020

Keywords

  • channelopathy
  • founder effect
  • mexiletine
  • myotonia
  • Na 1.4
  • sodium channel myotonia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Sodium Channel Myotonia Due to Novel Mutations in Domain I of Na<sub>v</sub>1.4'. Together they form a unique fingerprint.

  • Cite this