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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Cation Transport Proteins*
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Chromosome Mapping
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Chromosomes, Human, Pair 7
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DNA Mutational Analysis
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DNA-Binding Proteins*
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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Female
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Genetic Markers
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Humans
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Introns / genetics
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Long QT Syndrome / genetics*
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Male
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Molecular Sequence Data
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Organ Specificity
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Pedigree
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Point Mutation / genetics
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Polymorphism, Single-Stranded Conformational
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Potassium Channels / genetics*
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Potassium Channels, Voltage-Gated*
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RNA, Messenger / analysis
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Sequence Analysis, DNA
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Sequence Deletion / genetics
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Trans-Activators*
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Transcriptional Regulator ERG
Substances
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Cation Transport Proteins
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DNA-Binding Proteins
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ERG protein, human
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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Genetic Markers
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KCNH2 protein, human
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KCNH6 protein, human
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Potassium Channels
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Potassium Channels, Voltage-Gated
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RNA, Messenger
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Trans-Activators
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Transcriptional Regulator ERG