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: J Rosenfeld, K Sloan-Brown, A L George Jr
• Journal: Annals of neurology (Ann Neurol) Vol. 42 Issue 5 Pg. 811-4 (Nov 1997) ISSN: 0364-5134 [Print] United States
• PMID: 9392583 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium Channels

Topics

• Alleles
• DNA Mutational Analysis
• Exons (genetics)
• Family Health
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Muscle, Skeletal (chemistry, physiopathology)
• Myotonia Congenita (complications, genetics)
• Pain (etiology)
• Pedigree
• Phenotype
• Point Mutation
• Polymorphism, Single-Stranded Conformational
• Sodium Channels (genetics)