Translational approach to address therapy in myotonia permanens due to a new SCN4A mutation.

ABSTRACT:

Objective

We performed a clinical, functional, and pharmacologic characterization of the novel p.P1158L Nav1.4 mutation identified in a young girl presenting a severe myotonic phenotype.

Methods

Wild-type hNav1.4 channel and P1158L mutant were expressed in tsA201 cells for functional and pharmacologic studies using patch-clamp.

Results

The patient shows pronounced myotonia, slowness of movements, and generalized muscle hypertrophy. Because of general discomfort with mexiletine, she was given flecainide with satisfactory response. In vitro, mutant channels show a slower current decay and a rightward shift of the voltage dependence of fast inactivation. The voltage dependence of activation and slow inactivation were not altered. Mutant channels were less sensitive to me

SUBMITTER: Desaphy JF 

PROVIDER: S-EPMC4891212 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature