title: A mutation in HERG associated with notched T waves in long QT syndrome.
abstract: Long QT syndrome (LQT) is a genetically heterogeneous inherited disorder that causes sudden death from cardiac arrhythmia. Four loci have been mapped to chromosomes 3, 4, 7 and 11 and three specific mutated genes for LQT syndrome have been identified. LQT2 results from mutations in the human ether-a-gogo-related gene, HERG, a cardiac potassium channel, whose protein product likely underlies Ikd the rapidly activating delayed rectifier current. By SSCP analysis and direct sequencing, we determined a new missense mutation in the HERG coding sequence, a G to A transition at position 1681 resulting in the substitution of threonine for a highly conserved alanine at codon 561. This mutation, Ala561Thr, in the coding sequence of the fifth membrane-spanning domain (S5) of the HERG protein seems to convey a risk of cardiac events in affected family members. In addition to a prolonged T wave of low amplitude on the surface ECG, a distinctive biphasic T-wave pattern was found in the left precordial leads of all affected subjects with the Ala561Thr mutation regardless of age, gender and beta blocking therapy.
authors.affiliation: INSERM UR153, Hôpital Pitié-Salpétriére, Institut de Myologie, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Dausse
authors.forename: M
authors.initials: M
authors.lastname: Berthet
authors.forename: I
authors.initials: I
authors.lastname: Denjoy
authors.forename: X
authors.initials: X
authors.lastname: André-Fouet
authors.forename: C
authors.initials: C
authors.lastname: Cruaud
authors.forename: M
authors.initials: M
authors.lastname: Bennaceur
authors.forename: S
authors.initials: S
authors.lastname: Fauré
authors.forename: P
authors.initials: P
authors.lastname: Coumel
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: P
authors.initials: P
authors.lastname: Guicheney
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004562:Electrocardiography; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D008126:Lod Score; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree