Generation of patient-specific induced pluripotent stem cell lines with Type 2 Long QT Syndrome and the KCNH2 c.379C > T pathogenic variant

Lamia Goual; Elisa Bounasri; Marie Vincenti; Pascal Amédro; Romain Desprat; Florence Bernex; Jean-Marc Lemaitre; Jean-Luc Pasquié; Alain Lacampagne; Jérôme Thireau; Albano C Meli

doi:10.1016/j.scr.2023.103192

Generation of patient-specific induced pluripotent stem cell lines with Type 2 Long QT Syndrome and the KCNH2 c.379C > T pathogenic variant

Stem Cell Res. 2023 Oct:72:103192. doi: 10.1016/j.scr.2023.103192. Epub 2023 Aug 25.

Authors

Affiliations

¹ PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France.
² PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France; MicroBrain Biotech S.A.S., Marly Le-Roi, France.
³ PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France; Pediatric and Congenital Cardiology Department, M3C Regional Reference CHD Centre, Clinical Investigation Centre, Montpellier University Hospital, Montpellier, France.
⁴ Plateforme SAFE iPS, CHU Montpellier, IRMB, France.
⁵ RHEM, Réseau d'Histologie Expérimentale de Montpellier, Univ. Montpellier, BioCampus, CNRS, INSERM, Montpellier, France.
⁶ PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France; Department of Cardiology, CHU of Montpellier, Montpellier, France.
⁷ PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France. Electronic address: [email protected].
⁸ PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France. Electronic address: [email protected].

PMID: 37660555
DOI: 10.1016/j.scr.2023.103192

Abstract

Type 2 Long QT Syndrome (LQT2) is a rare genetic heart rhythm disorder causing life-threatening arrhythmias. We derived induced pluripotent stem cell (iPSC) lines from two patients with LQT2, aged 18 and 6, both carrying a heterozygous missense mutation on the 3rd and 11th exons of KCNH2. The iPSC lines exhibited normal genomes, expressed pluripotent markers, and differentiated into trilineage embryonic layers. These patient-specific iPSC lines provide a valuable model to study the molecular and functional impact of the hERG channel gene mutation in LQT2 and to develop personalized therapeutic approaches for this syndrome.

MeSH terms

Arrhythmias, Cardiac / metabolism
ERG1 Potassium Channel / genetics
Humans
Induced Pluripotent Stem Cells* / metabolism
Long QT Syndrome* / metabolism
Mutation

Substances

ERG1 Potassium Channel
KCNH2 protein, human