Generation of the human induced pluripotent stem cell (hiPSC) line PSMi007-A from a Long QT Syndrome type 1 patient carrier of two common variants in the NOS1AP gene.

Manuela Mura, Federica Pisano, Manuela Stefanello, Monia Ginevrino, Marina Boni, Federica Calabrò, Lia Crotti, Enza Maria Valente, Peter J Schwartz, Paul A Brink, Massimiliano Gnecchi

Journal: Stem cell research 2020;36():101416

PMID: 30878014

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Abstract

We generated human induced pluripotent stem cells (hiPSCs) from a symptomatic Long QT Syndrome (LQTS) type 1 patient, belonging to a South African (SA) founder population segregating the heterozygous mutation c.1022C > T p.A341V on the KCNQ1 gene. The patient is also homozygous for the two minor variants rs4657139 and rs16847548 on the NOS1AP gene, associated with greater risk for cardiac arrest and sudden death in LQTS mutation carriers of the founder population. hiPSCs, obtained using four retroviruses encoding the reprogramming factors OCT4, SOX2, cMYC and KLF4, display pluripotent stem cell characteristics, and can be differentiated into spontaneously beating cardiomyocytes (hiPSC-CMs).

Address: Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Molecular Medicine, Unit of Cardiology, Università degli studi di Pavia, Pavia, Italy.; Department of Molecular Medicine, Unit of Genetics, Università degli studi di Pavia, Pavia, Italy.; Neurogenetics Unit, Fondazione IRCCS Santa Lucia, Rome, Italy.; Laboratory of Oncohaematological Cytogenetic and Molecular Diagnostics, Division of Haematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.; Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy.; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.; Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.; Department of Internal Medicine, University of Stellenbosch, Tygerberg, South Africa.; Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Molecular Medicine, Unit of Cardiology, Università degli studi di Pavia, Pavia, Italy.; Department of Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: [email protected].

DOI: 10.1016/j.scr.2019.101416

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MeSH Terms: Adaptor Proteins, Signal Transducing, Cell Differentiation, Cell Line, Cellular Reprogramming Techniques, DNA Mutational Analysis, Female, Heterozygote, Homozygote, Humans, Induced Pluripotent Stem Cells, KCNQ1 Potassium Channel, Karyotype, Kruppel-Like Factor 4, Middle Aged, Romano-Ward Syndrome