Mutant sodium channel nav 1.7 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 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 - 88 . (canceled) 
     
     
         89 . A method for determining a subject's predisposition to a neurologic disorder associated with a sodium channel mutation, comprising the step of identifying mutations at one or more sites in regions of the nucleic acid sequence that encode an intracellular N-terminal region, an extracellular loop in domain I, an intracellular loop between domains I and II, an intracellular loop between domains II and III, an intramembrane region of domain II, or any combination thereof, such identified nucleotides indicating a predisposition to the neurologic disorder. 
     
     
         90 . The method of  claim 89 , wherein the mutation is present in the nucleic acid region encoding the intracellular N-terminus region of the subunit. 
     
     
         91 . The method of  claim 89 , wherein the mutation is present in the nucleic acid region encoding the extracellular loop of domain I of the subunit. 
     
     
         92 . The method of  claim 89 , wherein the mutation is present in the nucleic acid region encoding the intracellular loop between domains I and II of the subunit. 
     
     
         93 . The method of  claim 89 , wherein the mutation is present in the nucleic acid region encoding the intracellular loop between domains II and III of the subunit. 
     
     
         94 . The method of  claim 89 , wherein the mutation is present in the nucleic acid region encoding the intramembrane region of domain II of the subunit. 
     
     
         95 . The method of  claim 89 , wherein the step of identifying the mutations comprises comparing the nucleic acid sequence to a wild-type nucleic acid sequence. 
     
     
         96 . The method of  claim 95 , wherein the wild-type nucleic acid sequence encodes the amino acid sequence of SEQ ID NO: 38. 
     
     
         97 . The method of  claim 89 , 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. 
     
     
         98 . The method of  claim 89 , wherein the neurologic disorder is a seizure disorder. 
     
     
         99 . The method of  claim 98 , wherein the seizure disorder is a febrile seizure disorder. 
     
     
         100 . A method for determining a subject's predisposition to a neurologic disorder associated with a sodium channel mutation comprising comparing the subject's Nav1.7 haplotype with one or more reference haplotypes that correlate with the neurologic disorder, a similar haplotype in the subject's Nav1.7 haplotype as compared to the reference haplotype or haplotypes indicating a predisposition to the neurologic disorder. 
     
     
         101 . The method of claim  28 , wherein the neurologic disorder is a seizure disorder. 
     
     
         102 . The method of claim  29 , wherein the seizure disorder is a febrile seizure disorder.