Fig 1: HiPSC line derivation and validation APedigree of the patient family. Arrow: Index patient; index patient and mother are PLN p.Arg14del mutation carriers and were diagnosed with DCM.BSequencing of PLN patient-derived hiPSC (PLN p.Arg14del) and isogenic controls (PLNic) to confirm CRISPR/Cas9-mediated gene correction. Red box indicates codon for Arg14, and blue box indicates silent PAM (protospacer adjacent motif) mutation.C, DRelative PLN transcript level (normalized to ACTN2 and PLNic wt+mt) with PCR primers amplifying PLN wild type (wt) and p.Arg14del (mt), only wt or only p.Arg14del (mt). (C) Analysis of PLNic (n = 9 EHTs from 5 batches, each replicate consists of a pool of 1–2 EHTs from separate batches) and PLN p.Arg14del (n = 9 EHTs from 3 batches, each replicate consists of a pool of 2–4 EHTs from separate batches) EHTs, mean ± SEM. (D) Analysis of PLN p.Arg14del EHTs (n = 9 EHTs from 3 batches, each replicate consists of a pool of 2–4 EHTs from separate batches) and two independent failing heart patient samples from heterozygous PLN p.Arg14del mutation carriers (each n = 1 RNA sample, 2 separate PCR analysis), mean ± SEM.EImmunofluorescence of 2D hiPSC-CM from each genotype with antibodies against PLN (red) and SERCA2 (green) and DAPI staining of nuclei (blue); scale bar 20 µm.