Researchers at the National Hospital, Queen Square, London, UK, conducted automated DNA sequencing of the S4 regions of CACNA1S and SCN4A in 83 patients with hypokalemic periodic paralysis (HypoPP). CACNA1S mutations were identified in 64 cases, and SCN4A or other CACNA1S mutations in 10, including 4 with new mutations. All mutations neutralized arginine residues in S4 segments. The patients with new mutations had the typical HypoPP phenotype: onset of attacks of muscle paralysis in first or second decade, at night or early morning, and low serum potassium. The findings were consistent with the gating pore cation leak hypothesis of HypoPP, and arginine mutations in S4 segments are involved in 90% cases. [1]
COMMENT. In an editorial, Cannon SC proposes that the remaining 10% of HypoPP families with no identified mutation will also prove to be channelopathies, from a new class of molecular defect or different channel. [2]