Methods for identifying subjects susceptible to ataxic neurological disease

Abstract

In one aspect, the invention provides methods of identifying genetic mutations that are associated with ataxic neurological disease. The methods comprise identifying a difference between a nucleic acid sequence of a protein kinase C gamma gene from a mammalian subject exhibiting ataxia and a nucleic acid sequence of a protein kinase C gamma gene from a subject which is not exhibiting ataxia, wherein the difference is a genetic mutation associated with ataxic neurological disease. In another aspect, isolated nucleic acid molecules encoding protein kinase C gamma missense mutations are provided. In another aspect, a method of screening a subject to determine if the subject has a genetic predisposition to develop an ataxic neurological disease is provided. In another aspect, the invention provides kits for determining susceptibility or presence of ataxic neurological disease in a mammalian subject.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         1 . A method of screening a mammalian subject to determine if said subject has a genetic predisposition to develop an ataxic neurological disease, or is suffering from an ataxic neurological disease, said method comprising analyzing the nucleic acid sequence of a protein kinase C gamma gene in a mammalian subject to determine whether an identified genetic mutation that is associated with an ataxic neurological disease is present in the nucleic acid sequence, wherein the presence of an identified genetic mutation in the protein kinase C gamma gene that is associated with an ataxic neurological disease indicates that the mammalian subject has a genetic predisposition to develop an ataxic neurological disease or is suffering from an ataxic neurological disease. 
     
     
         2 . The method of  claim 1 , further comprising determining whether the mammalian subject is exhibiting ataxia. 
     
     
         3 . The method of  claim 1  wherein said nucleic acid sequence is analyzed by a method selected from the group consisting of direct sequencing, sequencing PCR-amplified DNA, DNA hybridization, and restriction fragment length polymorphism. 
     
     
         4 . The method of  claim 1  wherein said identified genetic mutation that is associated with ataxic neurological disease resides in exon 4 of the protein kinase C gamma gene. 
     
     
         5 . The method of  claim 1  wherein said identified mutation is a missense mutation. 
     
     
         6 . The method of  claim 1  wherein said identified mutation consists of an alteration in the protein kinase C gamma gene in the codon encoding an amino acid residue selected from the group consisting of amino acid residues 41, 101, 119, 127, 128, 361, and 597. 
     
     
         7 . The method of  claim 6  wherein the alteration at protein position 41 is R41P. 
     
     
         8 . The method of  claim 6  wherein the alteration at protein position 101 is H101Y. 
     
     
         9 . The method of  claim 6  wherein the alteration at protein position 119 is S119P. 
     
     
         10 . The method of  claim 6  wherein the alteration at protein position 127 is Q127R. 
     
     
         11 . The method of  claim 6  wherein the alteration at protein position 128 is G128D. 
     
     
         12 . The method of  claim 6  wherein the alteration at protein position 361 is S361G. 
     
     
         13 . The method of  claim 6  wherein the alteration at protein position 597 is R597S.