Patient-Specific Induced Pluripotent Stem-Cell Models for Long-QT Syndrome

Dermal fibroblasts were obtained from members of a family with the long-QT syndrome and from controls and were used to generate pluripotent stem cells, which were then directed to differentiate into cardiac myocytes. The cells recapitulated characteristics of the long-QT syndrome. The long-QT syndrome is a familial, usually autosomal dominant disease characterized by an abnormally prolonged ventricular repolarization phase and a propensity toward polymorphic ventricular tachycardia (often termed torsades de pointes) and sudden cardiac death. 1 – 3 At least 10 different forms of the long-QT syndrome have been described, but in approximately 45% of genotyped patients, the underlying causes are mutations in the KCNQ1 (also known as KVLQT1 or Kv7.1 ) gene, which encodes the pore-forming alpha subunits of the channels generating I Ks , an adrenergic-sensitive, slow outward potassium current. 2 , 4 , 5 This form of the long-QT syndrome is designated as . . .