Referenced in: none

Automatically associated channels: Kir2.3 , Nav1.4

Title: A novel muscle sodium channel mutation causes painful congenital myotonia.

Authors: J Rosenfeld, K Sloan-Brown, A L George

Journal, date & volume: Ann. Neurol., 1997 Nov , 42, 811-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9392583

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.