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.

Sodium Channel Myotonia Due to Novel Mutations in Domain I of Nav1.4 / S. Pagliarani, S. Lucchiari, M. Scarlato, E. Redaelli, A. Modoni, F. Magri, B. Fossati, S.C. Previtali, V.A. Sansone, M. Lecchi, M. Lo Monaco, G. Meola, G.P. Comi. - In: FRONTIERS IN NEUROLOGY. - ISSN 1664-2295. - 11(2020 Apr 29), pp. 255.1-255.9. [10.3389/fneur.2020.00255]

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

Pagliarani S.;Lucchiari S.;Redaelli E.;Magri F.;Fossati B.;Sansone V. A.;Meola G.;Comi G. P.
2020-04-29

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.
channelopathy; founder effect; mexiletine; myotonia; Na; v; 1.4; sodium channel myotonia
Settore MED/26 - Neurologia
FRONTIERS IN NEUROLOGY
Article (author)
File in questo prodotto:
File Dimensione Formato  
fneur-11-00255.pdf

accesso aperto

620.22 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/771931
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact