Mutant Sodium Channel Nav1.7 and Methods Related Thereto

Abstract

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 1.7 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 for selecting a therapy for a subject diagnosed with a seizure disorder, comprising detecting in a nucleic acid sample isolated from the subject one or more single nucleotide polymorphisms in the SCN9A gene. 
     
     
         2 . The method of  claim 1 , wherein the seizure disorder is a febrile seizure disorder. 
     
     
         3 . The method of  claim 1 , wherein the seizure disorder is Dravet syndrome. 
     
     
         4 . The method of  claim 1 , wherein identification of one or more single nucleotide polymorphisms in the SCN9A gene indicates a selected therapy other than a sodium channel blocker. 
     
     
         5 . The method of  claim 4 , wherein the selected therapy includes valproate. 
     
     
         6 . The method of  claim 4 , wherein the selected therapy includes benzodiazepines. 
     
     
         7 . The method of  claim 4 , wherein the selected therapy includes stiripentol. 
     
     
         8 . The method of  claim 4 , wherein the selected therapy includes toprimate. 
     
     
         9 . The method of  claim 4 , wherein the selected therapy includes levetiracetam. 
     
     
         10 . The method of  claim 4 , wherein the selected therapy excludes carbamazepine. 
     
     
         11 . The method of  claim 4 , wherein the selected therapy excludes phenyloin. 
     
     
         12 . The method of  claim 4 , wherein the selected therapy excludes lamotrigine. 
     
     
         13 . The method of  claim 1 , wherein the subject has a family member diagnosed with a seizure disorder and said family member is identified as having one or more Na v 1.7 mutations. 
     
     
         14 . The method of  claim 1 , wherein the method comprises detecting in the nucleic acid sample one or more single nucleotide polymorphisms in the SCN9A gene at the nucleotides encoding amino acid residues 228, 490, 519, 684, 699, 1160, or 1267 of Na v 1.7, or any combination thereof. 
     
     
         15 . The method of  claim 1 , further comprising detecting in the nucleic acid sample one or more mutations in the SCN1A gene. 
     
     
         16 - 75 . (canceled)