title: A novel muscle sodium channel mutation causes painful congenital myotonia.
abstract: Mutations in the skeletal muscle voltage-gated sodium channel alpha-subunit gene (SCN4A) have been associated with a spectrum of inherited nondystrophic myotonias and periodic paralyses. Most disease-associated SCN4A alleles occur in portions of the gene that encode the third and fourth repeat domains with the conspicuous absence of mutations in domain 1. Here we describe a family segregating an unusual autosomal dominant congenital myotonia associated with debilitating pain especially severe in the intercostal muscles. A novel SCN4A mutation causing the replacement of Val445 in the sixth transmembrane segment of domain 1 with methionine was discovered in all affected individuals and is the likely genetic basis for the syndrome. Myotonia was resistant to treatment; however, the most severely affected family member responded dramatically to the sodium channel blocking agent flecainide.
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rosenfeld
authors.forename: K
authors.initials: K
authors.lastname: Sloan-Brown
authors.forename: A L
authors.initials: AL
authors.lastname: George
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000503:physiopathology; D009224:Myotonia Congenita / Q000150:complications / Q000235:genetics*; D010146:Pain / Q000209:etiology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015222:Sodium Channels