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

• Published in: The New England journal of medicine Vol. 363; no. 15; pp. 1397 - 1409
• Main Authors: Moretti, Alessandra, Bellin, Milena, Welling, Andrea, Jung, Christian Billy, Lam, Jason T, Bott-Flügel, Lorenz, Dorn, Tatjana, Goedel, Alexander, Höhnke, Christian, Hofmann, Franz, Seyfarth, Melchior, Sinnecker, Daniel, Schömig, Albert, Laugwitz, Karl-Ludwig
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 07.10.2010
• Subjects: Action Potentials; Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Adult; Aged; Biological and medical sciences; Cardiac dysrhythmias; Cardiology. Vascular system; Cardiotonic Agents - pharmacology; Child; Electrocardiography; Female; Fibroblasts - cytology; Gene Expression; General aspects; Heart; Humans; Induced Pluripotent Stem Cells - physiology; Isoproterenol - pharmacology; KCNQ1 Potassium Channel - genetics; Male; Medical research; Medical sciences; Mutation; Mutation, Missense; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Pedigree; Phenotype; Potassium Channel Blockers - pharmacology; Potassium Channels - physiology; Reverse Transcriptase Polymerase Chain Reaction; Romano-Ward Syndrome - drug therapy; Romano-Ward Syndrome - genetics; Romano-Ward Syndrome - physiopathology; Stem cells; Human; Medicine; Arrhythmia; Heart block; Heart disease; Stem cell; Prolonged QT interval; Cardiovascular disease; Patient; Models; Conduction disorder
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0908679

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 . . .