Mutation in the beta2 nicotinic acetycholine receptor subunit associated with nocturnal frontal lobe epilepsy
OwnerHilary Philips, John Mulley +1inventors
InventorsHilary Philips, John Mulley, Samuel Berkovic
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Abstract
A point mutation in the β2 subunit of an nicotinic acetylcholine receptor providing a V287M transition is associated with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Claims68
An isolated DNA molecule encoding a mutant β-subunit of a mammalian nicotinic acetylcholine receptor (nAchR), wherein a mutation event selected from the group consisting of point mutations, deletions, insertions and rearrangements has occurred in the nucleotides encoding the M2 domain of the β-subunit of said mammalian nicotinic acetylcholine receptor and said mutation event disrupts the functioning of an assembled mammalian nicotinic acetylcholine receptor comprising the β-subunit so as to produce an epilepsy phenotype.
An isolated DNA molecule comprising the nucleotide sequence set forth in SEQ ID NO:1.
An isolated DNA molecule consisting of the nucleotide sequence set forth in SEQ ID NO:1.
An isolated polypeptide, said polypeptide being a mutant β-subunit of a mammalian nicotinic acetylcholine receptor (nAchR), wherein a mutation event selected from the group consisting of substitutions, deletions, insertions and rearrangements has occurred in the M2 domain and said mutation event disrupts the functioning of an assembled mammalian nicotinic acetylcholine receptor so as to produce an epilepsy phenotype.
An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.
An isolated polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:2.
An isolated polypeptide, said polypeptide being an assembled mammalian nicotinic acetylcholine receptor, comprising at least one α-subunit and at least one β-subunit, wherein a mutation event selected from the group consisting of substitutions, deletions, insertions and rearrangements has occurred in the M2 domain of a β-subunit and said mutation event disrupts the functioning of said assembled mammalian nicotinic acetylcholine receptor so as to produce an epilepsy phenotype.
A method of treating epilepsy, comprising administering a selective antagonist of the nicotinic acetylcholine receptor when it contains a mutation in the M2 domain of a β-subunit, said mutation being causative of epilepsy, to a subject in need of such treatment.
The use of a selective antagonist of the nicotinic acetylcholine receptor when it contains a mutation in the M2 domain of a β-subunit, said mutation being causative of epilepsy, in the manufacture of a medicament for the treatment of epilepsy.
A method for the diagnosis of epilepsy, comprising the steps of:
- (1) obtaining DNA from a subject suspected of epilepsy;
- and
- (2) comparing the DNA sequence of a β-subunit of the nicotinic acetylcholine receptor of said DNA to the DNA sequence of the corresponding β-subunit of the wild-type nicotinic acetylcholine receptor.
A method for the diagnosis of epilepsy, comprising the steps of:
- (1) obtaining the nicotinic acetylcholine receptor from a subject suspected of epilepsy;
- and
- (2) comparing a β-subunit of said receptor with the corresponding β-subunit of the wild-type nicotinic acetylcholine receptor.
Dependencies are inferred from the claim text.