Abstract
Potassium channels regulate electrical signaling and the ionic composition of biological fluids. Mutations in the three known genes of the KCNQ branch of the K+ channel gene family underlie inherited cardiac arrhythmias (in some cases associated with deafness) and neonatal epilepsy. We have now cloned KCNQ4, a novel member of this branch. It maps to the DFNA2 locus for a form of nonsyndromic dominant deafness. In the cochlea, it is expressed in sensory outer hair cells. A mutation in this gene in a DFNA2 pedigree changes a residue in the KCNQ4 pore region. It abolishes the potassium currents of wild-type KCNQ4 on which it exerts a strong dominant-negative effect. Whereas mutations in KCNQ1 cause deafness by affecting endolymph secretion, the mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hair cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Chromosome Mapping
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Cloning, Molecular
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DNA, Complementary / isolation & purification
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Ear, Inner / metabolism
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Female
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Gene Expression Regulation
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Genes, Dominant*
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Hair Cells, Auditory, Outer / metabolism*
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Hearing Loss, Sensorineural / genetics*
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Hearing Loss, Sensorineural / metabolism
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Humans
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KCNQ Potassium Channels
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Mice
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Molecular Sequence Data
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Mutation*
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Oocytes
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Pedigree
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Potassium Channels / biosynthesis*
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Potassium Channels / genetics*
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Potassium Channels / physiology
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Potassium Channels, Voltage-Gated*
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Xenopus laevis
Substances
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DNA, Complementary
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KCNQ Potassium Channels
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KCNQ4 protein, human
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Kcnq4 protein, mouse
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Potassium Channels
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Potassium Channels, Voltage-Gated
Associated data
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GENBANK/AF105202
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GENBANK/AF105203
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GENBANK/AF105204
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GENBANK/AF105205
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GENBANK/AF105206
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GENBANK/AF105207
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GENBANK/AF105208
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GENBANK/AF105209
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GENBANK/AF105210
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GENBANK/AF105211
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GENBANK/AF105212
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GENBANK/AF105213
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GENBANK/AF105214
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GENBANK/AF105215
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GENBANK/AF105216