Generation of an isogenic CRISPR/Cas9-corrected control induced pluripotent stem cell line from a patient with autosomal dominant catecholaminergic polymorphic ventricular tachycardia with a heterozygous variant in cardiac calsequestrin-2

Ginell N Ranpura; Mira Holliday; Serena Li; Samantha B Ross; Emma S Singer; Stuart T Fraser; Richard D Bagnall; Christopher Semsarian; Seakcheng Lim

doi:10.1016/j.scr.2024.103650

Generation of an isogenic CRISPR/Cas9-corrected control induced pluripotent stem cell line from a patient with autosomal dominant catecholaminergic polymorphic ventricular tachycardia with a heterozygous variant in cardiac calsequestrin-2

Stem Cell Res. 2024 Dec 31:83:103650. doi: 10.1016/j.scr.2024.103650. Online ahead of print.

Authors

Ginell N Ranpura¹, Mira Holliday¹, Serena Li¹, Samantha B Ross¹, Emma S Singer², Stuart T Fraser³, Richard D Bagnall², Christopher Semsarian⁴, Seakcheng Lim⁵

Affiliations

¹ Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
² Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Bioinformatics and Molecular Genetics Group at Centenary Institute, The University of Sydney, Sydney, Australia.
³ Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, Australia.
⁴ Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
⁵ Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. Electronic address: [email protected].

PMID: 39826349
DOI: 10.1016/j.scr.2024.103650

Abstract

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease characterised by adrenergic-induced arrhythmias. The leading causes of CPVT are pathogenic variants in cardiac ryanodine receptor 2 (RYR2) and rarely, in cardiac calsequestrin-2 (CASQ2) genes, which are major components of Ca²⁺ handling in cardiac myocytes. This resource builds upon an established induced pluripotent stem cell line generated from a family with autosomal dominant CPVT due to a heterozygous variant in CASQ2 c.539A > G, p.Lys180Arg (CIAUi003-A) (Ross et al., 2019). The current iPSC line was genetically modified using CRISPR/Cas9 to correct the pathogenic c.539A > G variant creating a CRISPR-corrected isogenic control line (CIAUi003-A-1).