Abstract
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, idiopathic partial epilepsy characterized by clusters of motor seizures occurring in sleep. We describe a mutation of the beta2 subunit of the nicotinic acetylcholine receptor, effecting a V287M substitution within the M2 domain. The mutation, in an evolutionary conserved region of CHRNB2, is associated with ADNFLE in a Scottish family. Functional receptors with the V287M mutation are highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. CHRNB2 is a new gene for idiopathic epilepsy, the second acetylcholine receptor subunit implicated in ADNFLE.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Amino Acid Sequence
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Amino Acid Substitution / genetics
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Animals
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Base Sequence
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Child
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Conserved Sequence
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Electric Conductivity
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Epilepsy, Frontal Lobe / genetics*
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Epilepsy, Frontal Lobe / metabolism
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Epilepsy, Frontal Lobe / physiopathology
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Female
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Genes, Dominant / genetics*
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Humans
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Male
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Molecular Sequence Data
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Mutation / genetics*
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Oocytes / drug effects
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Oocytes / metabolism
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Pedigree
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Protein Subunits
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Receptors, Nicotinic / genetics*
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Receptors, Nicotinic / metabolism
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Scotland
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Seizures / genetics
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Seizures / physiopathology
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Sleep Wake Disorders / genetics
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Sleep Wake Disorders / physiopathology
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Xenopus laevis
Substances
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Protein Subunits
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Receptors, Nicotinic
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nicotinic receptor beta2
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Acetylcholine