title: A new case of autosomal dominant myotonia associated with the V1589M missense mutation in the muscle sodium channel gene and its phenotypic classification.
abstract: We report a phenotype associated with the Val1589Met substitution in SCN4A gene in a French family which would be better classified as paramyotonia congenita. The proband was a 48-year-old woman, who described muscle stiffness and occasional flaccid weakness, both symptoms being induced by exercise, cold and heat. Severe muscle stiffness affected facial, oropharyngeal and limb muscles leading to transient paralysis of these muscles. One sister, two nephews and the son of the proband had similar symptoms. Molecular analysis of the muscle sodium channel gene (SCN4A) by nucleotide sequencing revealed a G-to-A transition of cDNA nucleotide at position 4765 predicting a substitution of methionine for valine at position 1589. This shows that the Val1589Met mutation in the SCN4 gene may cause different phenotypes, either potassium-aggravated myotonia or paramyotonia congenita. Familial or individual factors other than the missense mutation per se influence the expression of the disease in sodium channel disorders.
authors.affiliation: Clinique Neurologique, Service de Neurologie D, Hôpital Roger Salengro, CHRU Lille, 59037 Lille Cedex, France. d-ferriby@chru-lille.fr
authors.forename: D
authors.initials: D
authors.lastname: Ferriby
authors.forename: T
authors.initials: T
authors.lastname: Stojkovic
authors.forename: D
authors.initials: D
authors.lastname: Sternberg
authors.forename: J-F
authors.initials: JF
authors.lastname: Hurtevent
authors.forename: J-P
authors.initials: JP
authors.lastname: Hurtevent
authors.forename: P
authors.initials: P
authors.lastname: Vermersch
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D025063:Chromosome Disorders / Q000235:genetics; D003080:Cold Temperature / Q000009:adverse effects; D004252:DNA Mutational Analysis; D015444:Exercise / Q000502:physiology; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020125:Mutation, Missense / Q000235:genetics*; D020967:Myotonic Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D062553:NAV1.4 Voltage-Gated Sodium Channel; D010243:Paralysis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels