A PROPOSED MUTATION, VAL781ILE, ASSOCIATED WITH HYPERKALEMIC PERIODICPARALYSIS AND CARDIAC DYSRHYTHMIA IS A BENIGN POLYMORPHISM

Twenty different point mutations have been identified in the gene codi ng for the alpha subunit of the adult skeletal muscle sodium channel i n families with hyperkalemic periodic paralysis, paramyotonia congenit a, and the potassium-aggravated myotonias. One novel mutation (Val781I le) was reported in an adopted boy with potassium-sensitive weakness a nd cardiac dysrhythmia. The confidence in establishing this rare amino acid substitution as a causative mutation was limited by the absence of family members for segregation analysis. Functional expression stud ies herein show that Val781Ile is most likely a benign polymorphism an d not a disease-associated mutation.