Generation of a set of genetically modified long QT syndrome induced pluripotent stem cell lines carrying knock-in variants rs120074178 (KCNQ1 c.569G > A; p.Arg190Gln) and rs137854600 (SCN5A c.4865G > A; p.Arg1622Gln) and isogenic control lines

Nayara Sousa da Silva; Agnieszka D'Antonio-Chronowska; Reyna Hernandez-Benitez; Angelina Rose McCarron; Esra Karaca; Kai Fang; Juan Carlos Izpisua Belmonte; Athanasia D Panopoulos; Keiichiro Suzuki; Kelly A Frazer

doi:10.1016/j.scr.2025.103755

Generation of a set of genetically modified long QT syndrome induced pluripotent stem cell lines carrying knock-in variants rs120074178 (KCNQ1 c.569G > A; p.Arg190Gln) and rs137854600 (SCN5A c.4865G > A; p.Arg1622Gln) and isogenic control lines

Stem Cell Res. 2025 Sep:87:103755. doi: 10.1016/j.scr.2025.103755. Epub 2025 Jun 18.

Affiliations

¹ University of California, San Diego, Institute for Genomic Medicine, La Jolla, CA, USA.
² University of California, San Diego, Department of Pediatrics, La Jolla, CA, USA.
³ Altos Labs, Inc., San Diego, CA, USA.
⁴ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁵ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁶ Institute for Advanced Co-Creation Studies, Osaka University, Toyonaka, Osaka, Japan; Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, Japan; Graduate School of Frontier Bioscience, Osaka University, Suita, Osaka, Japan.
⁷ University of California, San Diego, Institute for Genomic Medicine, La Jolla, CA, USA; University of California, San Diego, Department of Pediatrics, La Jolla, CA, USA. Electronic address: kafrazer@health.ucsd.edu.

PMID: 40561734
DOI: 10.1016/j.scr.2025.103755

Abstract

Long QT syndrome (LQTS) is an inherited channelopathy characterized by life-threatening arrhythmias. LQTS has many subtypes defined by the gene that contains the mutation, including LQT1 (KCNQ1), LQT2 (KCNH2), and LQT3 (SCN5A). Here, we used CRISPR/Cas9 technology to generate five isogenic human induced pluripotent stem cell (iPSC) lines, one line harboring an LQT1 variant rs120074178 (KCNQ1 c.569G > A), two lines harboring an LQT3 variant rs137854600 (SCN5A c.4865G > A), and two derived control lines.

MeSH terms

CRISPR-Cas Systems
Cell Line
Gene Knock-In Techniques
Humans
Induced Pluripotent Stem Cells* / cytology
Induced Pluripotent Stem Cells* / metabolism
KCNQ1 Potassium Channel* / genetics
Long QT Syndrome* / genetics
Long QT Syndrome* / metabolism
Long QT Syndrome* / pathology
NAV1.5 Voltage-Gated Sodium Channel* / genetics
NAV1.5 Voltage-Gated Sodium Channel* / metabolism

Substances

NAV1.5 Voltage-Gated Sodium Channel
SCN5A protein, human
KCNQ1 Potassium Channel
KCNQ1 protein, human