title: Patient with syncope and LQTS carrying a mutation in the PAS domain of the hERG1 channel.
abstract: We report the case of a woman with syncope and persistently prolonged QTc interval. Screening of congenital long QT syndrome (LQTS) genes revealed that she was a heterozygous carrier of a novel KCNH2 mutation, c.G238C. Electrophysiological and biochemical characterizations unveiled the pathogenicity of this new mutation, displaying a 2-fold reduction in protein expression and current density due to a maturation/trafficking-deficient mechanism. The patient's phenotype can be fully explained by this observation. This study illustrates the importance of performing genetic analyses and mutation characterization when there is a suspicion of congenital LQTS. Identifying mutations in the PAS domain or other domains of the hERG1 channel and understanding their effect may provide more focused and mutation-specific risk assessment in this population.
authors.affiliation: Department of Clinical Research, University of Bern, Switzerland.
authors.forename: Liliana Sintra
authors.initials: LS
authors.lastname: Grilo
authors.forename: Jürg
authors.initials: J
authors.lastname: Schläpfer
authors.forename: Florence
authors.initials: F
authors.lastname: Fellmann
authors.forename: Hugues
authors.initials: H
authors.lastname: Abriel
mesh_terms: D003937:Diagnosis, Differential; D004452:Echocardiography; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005080:Exercise Test; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D013575:Syncope / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human