Mutant sodium channel Na
Described are mutant Na v 1.7 sodium channel alpha-subunits and nucleic acid sequences encoding such mutants. Further described are methods for characterizing a nucleic acid sequence that encodes a Na v 1 sodium channel alpha-subunit, methods for determining a Na v 1.7 haplotype, methods for determining a subject's predisposition to a neurologic disorder associated with a sodium channel mutation, and methods of identifying a compound that modulates mutant Na v 1.7 sodium channels. Other materials, compositions, articles, devices, and methods relating to mutant Na v 1.7 sodium channels are also described herein.
1. A method of characterizing a nucleic acid sequence that encodes a Na v 1.7 sodium channel alpha subunit, comprising the step of identifying mutations in regions of the nucleic acid sequence that encode an intracellular loop between domains I and II, wherein the mutation encodes amino acid residue which corresponds to amino acid residue 641 of human Na v 1.7 sodium channel alpha subunit, such identified nucleotides indicating the character of the nucleic acid sequence.
2. The method of claim 1 , wherein the encoded amino acid residue is tyrosine.
3. The method of claim 1 , wherein the step of identifying the mutations comprises comparing the nucleic acid sequence to a wild-type nucleic acid sequence.
4. The method of claim 3 , wherein the wild-type nucleic acid sequence encodes the amino acid sequence of SEQ ID NO: 38.
5. The method of claim 1 , wherein the identifying step comprises obtaining a biological sample and testing the sample to identify the nucleotides at the mutations sites of the nucleic acid contained therein.
6. The method of claim 5 , wherein the sample is tested by sequencing or probing the nucleic acid.
7. The method of claim 6 , wherein the testing step comprises the step of amplifying the nucleic acid contained in the sample.
8. The method of claim 7 , wherein the testing step further comprises sequencing the amplified nucleic acid.
9. The method of claim 7 , wherein the amplifying step comprises a polymerase chain reaction (PCR).
10. The method of claim 7 , wherein the amplifying step comprises contacting the nucleic acid with a primer comprising one or more of the sequences of SEQ ID NOs: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, and 31.
11. A method for determining a Na v 1.7 haplotype in a human subject comprising identifying one or more nucleotides encoding amino acid residues 641, wherein the nucleotide or nucleotides indicated the haplotype.
12. A method for determining a subject's predisposition to a neurologic disorder associated with a sodium channel mutation comprising comparing the subject's Na v 1.7 haplotype with one or more reference haplotypes that correlate with the neurologic disorder, a similar haplotype in the subject's Na v 1.7 haplotype as compared to the reference haplotype or haplotypes indicating a predisposition to the neurologic disorder, wherein the reference haplotype comprises nucleotides that encode mutations which corresponds to amino acid residue 641 of human Na v 1.7 sodium channel alpha subunit.
13. The method of claim 12 , wherein the neurologic disorder is a seizure disorder.
14. The method of claim 13 , wherein the seizure disorder is a febrile seizure disorder.