Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1.
Long QT syndrome (LQT) is a cardiac disorder causing syncope and sudden death from arrhythmias. LQT is characterized by prolongation of the QT interval on electrocardiogram, an indicationof abnormal cardiac repolarization. Mutations in KVLQT1, HERG, SCN5A, and KCNE1, genes encoding cardiac ion channels, cause LQT. Here, we define thecomplete genomic structure of three LQT genesand use this information to identify disease-associated mutations. KVLQT1 is composed of 16 exonsand encompasses approximately 400 kb. HERG consists of 16 exons and spans 55 kb. Three exons make up KCNE1. Each intron of these genes contains the invariant GT and AG at the donor and acceptor splice sites, respectively. Intron sequences were used to design primer pairs for the amplification of all exons. Familial and sporadic cases affected bymutations in KVLQT1, HERG, and KCNE1 can nowbe genetically screened to identify individuals at risk of developing this disorder. This work has clinical implications for presymptomatic diagnosis and therapy.
Cardiology Division, University of Utah, Salt Lake City, Utah, 84112, USA.
I
I
Splawski
J
J
Shen
K W
KW
Timothy
G M
GM
Vincent
M H
MH
Lehmann
M T
MT
Keating
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D027682:Cation Transport Proteins; D017931:DNA Primers; 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; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C059983:potassium channel protein I(sk)