Long QT syndrome

Diseased iPSC lines - Long QT syndrome

Long QT syndrome (LQTS) is an arrhythmic disease leading to an increased risk of ventricular tachycardia and sudden death. The congenital form of the syndrome is caused by mutations in proteins involved in cardiomyocyte ionic channel functioning. Using cardiomyocytes derived from patient-specific iPSCs is the most promising approach to study LQTS molecular mechanisms and to search for effective therapy methods. Using episomal vectors, we generated iPSC lines from fibroblasts of two LQTS patients carrying p.V254M mutation in KCNQ1 and p.T613M mutation in KCNH2. The iPSC lines can be used for modeling long QT syndrome types 1 and 2 that are the most common forms of the congenital LQTS.

Diseased iPSC lines - Long QT syndrome
Characterization of an iPSC line derived from a long QT syndrome patient carrying p.T613M mutation in KCNH2. A. Morphology of the iPSC colonies (Scale bar – 200 μm). B. Immunofluorescent staining for pluripotency markers NANOG, OCT4, TRA-1-60, SSEA4 (Scale bar – 100 μm). C. Immunofluorescent staining for differentiation markers, NF200 (ectoderm), αSMA (mesoderm), HNF4α (endoderm), after spontaneous in vitro differentiation of the iPSC line (Scale bar – 100 μm). D. Mutation analysis. Sanger sequencing of exon 7 of KCNH2 in the iPSC lines and healthy donor. Heterozygous p.T613M (c.1838C>T) mutation is indicated by a black arrow.

Long QT syndrome (LQTS) is an arrhythmic disease leading to an increased risk of ventricular tachycardia and sudden death. The congenital form of the syndrome is caused by mutations in proteins involved in cardiomyocyte ionic channel functioning. Using cardiomyocytes derived from patient-specific iPSCs is the most promising approach to study LQTS molecular mechanisms and to search for effective therapy methods. Using episomal vectors, we generated iPSC lines from fibroblasts of two LQTS patients carrying p.V254M mutation in KCNQ1 and p.T613M mutation in KCNH2. The iPSC lines can be used for modeling long QT syndrome types 1 and 2 that are the most common forms of the congenital LQTS.