Pathogenic KCNH2-G53S variant in the PAS domain influences the electrophysiological phenotype in long QT syndrome type 2.

ABSTRACT:

Background

Long QT syndrome type 2 (LQT2) is an arrythmia caused by loss-of-function mutations in KCNH2, leading to impaired Kv11.1 channel function.

Objective

To better understand LQT2, we examined the electrophysiological differences related to the G53S variant, which is located within the PAS domain of KCNH2, using patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs).

Methods

We generated hiPSC-CMs from a patient harboring the KCNH2^G53S variant and a healthy control using non-integrative Sendai virus-mediated reprogramming. Their electrophysiological properties were assessed using microelectrode arrays (MEA), and Ca²⁺ dynamics were characterized using Fluo-4 dye.

Results

The patient harboring K

SUBMITTER: Mun D 

PROVIDER: S-EPMC12014601 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature