Key result
CRISPR/Cas9 successfully corrects the c.1643delG PKP2 mutation in ACM patient-derived iPSCs.
Why the study?
Arrhythmogenic cardiomyopathy is a rare genetic cardiac disease linked to desmosomal gene mutations, with unclear in vitro models for the c.1643delG PKP2 mutation.
Patient-derived, CRISPR-corrected hiPSC lines enable ACM modeling; leaves open any clinical translation of gene editing.
Arrhythmogenic Cardiomyopathy (ACM) is a rare genetic cardiac disease predominantly associated with mutations in genes of the desmosomes and characterized by arrhythmia and fibro-fatty replacement of the myocardium. We generated human induced pluripotent stem cells (hiPSCs) from one patient affected by ACM carrying the heterozygous c.1643delG (p.G548VfsX15) PKP2 mutation and then corrected the mutation using CRISPR/Cas9 technology. Both original and corrected hiPSC lines showed typical morphology of pluripotent cells, expressed pluripotency markers, displayed a normal karyotype, and differentiated towards the three germ layers. This isogenic hiPSC pair can be used to study the role of the c.1643delG PKP2 mutation in vitro.
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Meraviglia et al. (2021) studied Arrhythmogenic Cardiomyopathy (ACM) (n=1). CRISPR/Cas9 mutation correction vs. Uncorrected hiPSC line was evaluated on Typical morphology, pluripotency markers, normal karyotype, and differentiation capability. Human induced pluripotent stem cells from an ACM patient with the c.1643delG PKP2 mutation were successfully corrected using CRISPR/Cas9 to create an isogenic pair for in vitro studies.
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