Key result
Novel patient-derived iPSC lines successfully model a de novo fetal KCNH2 variant.
These newly generated patient-specific and parental control hiPSC lines provide an in vitro model for studying congenital long QT syndrome caused by a de novo KCNH2 (p.Asn633Ser) mutation and testing potential personalized therapies.
These fetal LQT2 iPSC lines enable in vitro modeling; leaves open clinical translation for personalized therapy.
Long QT syndrome (LQTS) is a channelopathy that predisposes affected individuals to ventricular arrhythmias and cardiac arrest. Here, a human induced pluripotent stem cell (hiPSC) line was generated from amniotic fluid cells (AFCs) of a 32-week fetus diagnosed with LQTS. Additionally, two iPSC lines were generated from peripheral blood mononuclear cells (PBMCs) of the fetus's healthy biological parents. Genome sequencing revealed that the fetus with LQTS carried a de novo KCNH2 variant, c.1898A > G (p.Asn633Ser). All three iPSC lines demonstrated normal morphology, karyotyping, and pluripotency. These iPSC lines provide a valuable in vitro model for LQTS caused by KCNH2 mutations.
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Putra et al. (2025) studied Congenital long QT syndrome (LQTS) caused by a de novo KCNH2 variant (c.1898A > G, p.Asn633Ser) (n=3). Somatic cell reprogramming via non-integrating Sendai virus carrying human Yamanaka factors (OCT3/4, SOX2, KLF4, c-MYC) vs. Parental wild-type hiPSC lines (USFi006-A and USFi007-A) and control hiPSC line (CUSO-2) was evaluated on Generation and characterization of human induced pluripotent stem cell (hiPSC) lines (morphology, karyotype, pluripotency marker expression, trilineage differentiation, and KCNH2 genotype confirmation). Three human iPSC lines generated from a 32-week fetus with a de novo KCNH2 c.1898A>G variant and her two healthy parents showed normal karyotypes, pluripotency, and trilineage differentiation.
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