title: Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome.
abstract: Long QT syndrome (LQTS), is an inherited cardiac disorder in which ventricular tachyarrhythmias predispose affected individuals to syncope, seizures, and sudden death. Characteristic electrocardiographic findings include a prolonged QT interval, T wave alternans, and notched T waves. We have screened LQTS patients from 89 families for mutations in the pore region of HERG , the K+ channel gene previously associated with chromosome 7-linked LQT2. In six unrelated LQTS kindreds, single-strand conformation polymorphism analyses identified aberrant conformers in all affected family members. These conformers were not seen in over 100 unaffected, unrelated control individuals, suggesting that they represent pathogenic LQTS mutations. DNA sequence analyses of the aberrant conformers demonstrated that they reflect five different missense mutations: V612L, A614V, N629D, N629S, and N633S. The missense mutation A614V was found in two unrelated families. Further functional studies will be required to determine what effect each of these changes may have on HERG channel function.
authors.affiliation: Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Satler
authors.forename: M R
authors.initials: MR
authors.lastname: Vesely
authors.forename: P
authors.initials: P
authors.lastname: Duggal
authors.forename: G S
authors.initials: GS
authors.lastname: Ginsburg
authors.forename: A H
authors.initials: AH
authors.lastname: Beggs
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D027682:Cation Transport Proteins; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014481:United States
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; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG