title: Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects.
abstract: Analysis of the entire coding region of the HERG gene of 39 Finnish LQTS patients revealed eight mutations, six of which are hitherto unreported. All these mutations are located in the evolutionarily conserved regions of HERG, including the transmembrane domains (P451L, Y569H, 1631delAG, G584S, G601S, T613M) and the cytoplasmic N-terminus (453delC, R176W) of the channel. Our present and earlier results suggest that the LQT2 subtype accounts for approximately 20-30% of LQTS cases in Finland. We also report the first common amino acid polymorphism (K897T) of the HERG channel, with allele frequencies of 0.84 and 0.16. Investigation of 170 genetically homogenous LQT1 patients suggests that this polymorphism may influence QT interval in female individuals.
authors.affiliation: Department of Medicine, University of Helsinki, FIN-00290 Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Laitinen
authors.forename: H
authors.initials: H
authors.lastname: Fodstad
authors.forename: K
authors.initials: K
authors.lastname: Piippo
authors.forename: H
authors.initials: H
authors.lastname: Swan
authors.forename: L
authors.initials: L
authors.lastname: Toivonen
authors.forename: M
authors.initials: M
authors.lastname: Viitasalo
authors.forename: J
authors.initials: J
authors.lastname: Kaprio
authors.forename: K
authors.initials: K
authors.lastname: Kontula
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics*; D027682:Cation Transport Proteins; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000032:analysis / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017384:Sequence Deletion; 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; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG