Article: article from journal or magazin.
New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Dec 14
BACKGROUND: Periodic paralysis is classified into hypokalemic (hypoPP) and hyperkalemic (hyperPP) periodic paralysis according to variations of blood potassium levels during attacks. OBJECTIVE: To describe new mutations in the muscle sodium channel gene SCN4A that cause periodic paralysis. METHODS: A thorough clinical, electrophysiologic, and molecular study was performed of four unrelated families who presented with periodic paralysis. RESULTS: The nine affected members had episodes of muscle weakness reminiscent of both hyperPP and hypoPP. A provocative test with potassium chloride was positive in two patients. However, repeated and carefully performed tests of blood potassium levels during attacks resulted in normal potassium levels. Remarkably, two patients experienced hypokalemic episodes of paralysis related to peculiar provocative factors (corticosteroids and thyrotoxicosis). Similarly to hyperPP, electromyography in nine patients revealed increased compound muscle action potentials after short exercise and a delayed decline during rest after long exercise as well as myotonic discharges in one patient. With use of molecular genetic analysis of the gene SCN4A, three new mutations were found affecting codon 675. They resulted in an amino acid substitution of a highly conserved arginine (R) to either a glycine (G), a glutamine (Q), or a tryptophan (W). Interestingly, hypoPP is caused by both mutations affecting nearby codons as well as the change of an arginine into another amino acid. CONCLUSION: A potassium-sensitive and normokalemic type of periodic paralysis caused by new SCN4A mutations at codon 675 is reported.
Acetazolamide/therapeutic use Action Potentials Adolescent Adrenal Cortex Hormones/adverse effects Adult *Amino Acid Substitution Child, Preschool Codon/*genetics DNA Mutational Analysis Electromyography Exercise Test Female Humans Hypokalemic Periodic Paralysis/blood/drug therapy/etiology/*genetics Infant Male *Mutation, Missense Pedigree *Point Mutation Potassium/blood Potassium Chloride/diagnostic use Sodium Channels/deficiency/*genetics Thyrotoxicosis/complications
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