A proposed mutation, Val781Ile, associated with hyperkalemic periodic paralysis and cardiac dysrhythmia is a benign polymorphism.
Twenty different point mutations have been identified in the gene coding for the alpha subunit of the adult skeletal muscle sodium channel in families with hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium-aggravated myotonias. One novel mutation (Val(781)Ile) was reported in an adopted boy with potassium-sensitive weakness and 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 studies herein show that Val(781)Ile is most likely a benign polymorphism and not a disease-associated mutation.
Green
D S
DS
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Hayward
L J
LJ
George
A L
AL
Cannon
S C
SC
D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D002460:Cell Line; D002648:Child; D006801:Humans; D006947:Hyperkalemia / Q000235:genetics*; D007532:Isoleucine; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D014633:Valine
D011994:Recombinant Proteins; D015222:Sodium Channels; D007532:Isoleucine; D014633:Valine