A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.

ABSTRACT:

Objective

To determine the molecular basis of a complex phenotype of congenital muscle weakness observed in an isolated but consanguineous patient.

Methods

The proband was evaluated clinically and neurophysiologically over a period of 15 years. Genetic testing of candidate genes was performed. Functional characterization of the candidate mutation was done in mammalian cell background using whole cell patch clamp technique.

Results

The proband had fatigable muscle weakness characteristic of congenital myasthenic syndrome with acute and reversible attacks of most severe muscle weakness as observed in periodic paralysis. We identified a novel homozygous SCN4A mutation (p.R1454W) linked to this recessively inherited phenotype. The p.R1454W substitution induced an importan

SUBMITTER: Habbout K 

PROVIDER: S-EPMC4731685 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature