Jervell and Lange-Nielsen Syndrome Related Clinical Genetics and Experimental Models

Jervell and Lange-Nielsen syndrome (JLNS) is defined by electrocardiographic QT prolongation and sensorineural hearing loss, caused by homozygous or compound heterozygous variants in KCNQ1 and/or KCNE1. KCNQ1 encodes the alpha subunit Kv7.1 of the ion channels accountable for slow delayed rectifier potassium currents (IKs), whereas KCNE1 encodes the beta subunit mink, which modulates the function of IKs. This review comprehensively summarizes the clinical features and genetic traits of JLNS. The pathogenicity of the amino acid substitutions in Kv7.1 and mink was assessed using AlphaFold. Furthermore, we systematically evaluated recent progress in experimental models of JLNS as well as phenotypic characterization and mechanistic studies across these experimental platforms, encompassing nonexcitable cell systems, genetically engineered murine models, and patient-specific induced pluripotent cell-derived cardiomyocytes and inner ear hair cells.