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A novel muscle sodium channel mutation causes painful congenital myotonia
Author(s) -
Rosenfeld Jeffrey,
SloanBrown Karen,
George Alfred L.
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410420520
Subject(s) - myotonia , mutation , sodium channel , genetics , channelopathy , skeletal muscle , exon , flecainide , medicine , biology , gene , chemistry , sodium , organic chemistry , myotonic dystrophy , atrial fibrillation
Mutations in the skeletal muscle voltage‐gated sodium channel α‐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 Val 445 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.