title: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
abstract: To identify genes involved in cardiac arrhythmia, we investigated patients with long QT syndrome (LQT), an inherited disorder causing sudden death from a ventricular tachyarrythmia, torsade de pointes. We previously mapped LQT loci on chromosomes 11 (LQT1), 7 (LQT2), and 3 (LQT3). Here, linkage and physical mapping place LQT2 and a putative potassium channel gene, HERG, on chromosome 7q35-36. Single strand conformation polymorphism and DNA sequence analyses reveal HERG mutations in six LQT families, including two intragenic deletions, one splice-donor mutation, and three missense mutations. In one kindred, the mutation arose de novo. Northern blot analyses show that HERG is strongly expressed in the heart. These data indicate that HERG is LQT2 and suggest a likely cellular mechanism for torsade de pointes.
authors.affiliation: Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112.
authors.forename: M E
authors.initials: ME
authors.lastname: Curran
authors.forename: I
authors.initials: I
authors.lastname: Splawski
authors.forename: K W
authors.initials: KW
authors.lastname: Timothy
authors.forename: G M
authors.initials: GM
authors.lastname: Vincent
authors.forename: E D
authors.initials: ED
authors.lastname: Green
authors.forename: M T
authors.initials: MT
authors.lastname: Keating
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007438:Introns / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005819:Genetic Markers; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG