Novel de novo mutation in the KCNJ2 gene in a patient with Andersen-Tawil syndrome

Abstract

Andersen-Tawil syndrome is a rare autosomal-dominant disease characterized by episodic muscle weakness, cardiac arrhythmias, and dysmorphic features. Mutations in the KCNJ2 gene (which encodes an inward-rectifying potassium channel protein, Kir2.1) have been reported to be responsible for this disorder. Reported here is a novel de novo mutation in the KCNJ2 gene in a patient with Andersen-Tawil syndrome. This mutation predicts the substitution of alanine for glycine at position 146 (Gly146Ala, c.437G > C) of Kir2.1 and is located at the extracellular pore loop region that serves as a principal ion-selective filter. The patient did not respond to acetazolamide, but experienced an improvement of the paralytic symptoms on treatment with a combination of spironolactone, amiloride, and potassium supplements.