Lafora's disease gene

Abstract

A novel gene (EPM2B) that is mutated in humans and dogs with Lafora's disease is described.

What is claimed is: 
     
         1 . An isolated nucleic acid molecule encoding a protein with a RING-finger domain and 6 NHL-motifs wherein the protein is associated with Lafora's disease. 
     
     
         2 . A nucleic acid according to  claim 1 , having a sequence comprising SEQ ID NO:1. 
     
     
         3 . An isolated nucleic acid molecule according to  claim 1 , comprising
 (a) a nucleic acid sequence comprising SEQ ID NO:1, wherein T can also be U;   (b) a nucleic acid sequence complementary to (a);   (c) a nucleic acid sequence that has substantial sequence homology to a nucleic acid sequence of (a) or (b);   (d) a nucleic acid sequence that is an analog of a nucleic acid sequence of (a), (b) or (c); or   (e) a nucleic acid sequence that hybridizes to a nucleic acid sequence of (a), (b), (c) or (d) under stringent hybridization conditions.   
     
     
         4 . A method of detecting Lafora's disease in a human comprising detecting a mutation in a nucleic acid sequence in a sample from a mammal, wherein said nucleic acid sequence is an isolated nucleic acid molecule encoding a protein with a RING-finger domain and 6 NHL-motifs, and wherein the protein is associated with Lafora's disease, wherein the mutation is selected from the group consisting of:
 a) a C to G change at nucelotide number 205 in the EPM2B gene sequence comprising SEQ ID NO:1;   b) a T to A change at nucleotide number 76 in the EPM2B gene sequence comprising SEQ ID NO:1;   c) a deletion of nucleotides GA at nucleotide positions 1048 and 1049 in the EPM2B gene sequence comprising SEQ ID NO:1;   d) a deletion of nucleotides AG at nucleotide positions 468 and 469 in the EPM2B gene sequence comprising SEQ ID NO:1;   e) a deletion of nucleotide G at nucleotide number 992 in the EPM2B gene sequence comprising SEQ ID NO:1;   f) a deletion of 10 by at nucleotide positions 373 to 382 in the EPM2B gene sequence comprising SEQ ID NO:1;   g) a deletion of 32 by at nucleotide positions 661 to 692 in the EPM2B gene sequence comprising SEQ ID NO:1;   h) a T to C change at nucleotide number 260 in the EPM2B gene sequence comprising SEQ ID NO:1;   i) a A to C change at nucleotide number 905 in the EPM2B gene sequence comprising SEQ ID NO:1;   j) a T to C change at nucleotide number 98 in the EPM2B gene sequence comprising SEQ ID NO:1;   k) an insert of 2 Ts at nucleotide number 892 in the EPM2B gene sequence comprising SEQ ID NO:1;   l) a G to A change at nucleotide number 436 in the EPM2B gene sequence comprising SEQ ID NO:1;   m) a deletion of nucleotide T at nucleotide number 1100 in the EPM2B gene sequence comprising SEQ ID NO:1;   n) a deletion of nucleotide T at nucleotide position 606 in the EPM2B gene sequence comprising SEQ ID NO:1;   o) a A to T change at nucleotide number 923 in the EPM2B gene sequence comprising SEQ ID NO:1;   p) a G to T change at nucleotide number 580 in the EPM2B gene sequence comprising SEQ ID NO:1;   q) a G to T change at nucleotide number 199 in the EPM2B gene sequence comprising SEQ ID NO:1;   r) a G to A change at nucleotide number 838 in the EPM2B gene sequence comprising SEQ ID NO:1;   s) a C to T change at nucleotide number 676 in the EPM2B gene sequence comprising SEQ ID NO:1;   t) a deletion of nucleotide A at nucleotide position 468 in the EPM2B gene sequence comprising SEQ ID NO:1; and   u) a deletion of nucleotide C at nucleotide position 204 in the EPM2B gene sequence comprising SEQ ID NO:1.   
     
     
         5 . An isolated protein containing a RING-finger domain and six NHL domains which protein is associated with Lafora's disease. 
     
     
         6 . A protein according to  claim 5 , having the amino acid sequence comprising SEQ ID NO:2. 
     
     
         7 . A method for detecting Lafora's disease comprising detecting a mutation in a protein according to  claim 5 . 
     
     
         8 . A method according to  claim 7 , comprising detecting a mutation in the EPM2B protein as indicated in Table 1. 
     
     
         9 . A kit for carrying out the method of  claim 4 , comprising reagents for the detection of a mutation in a nucleic acid sequence comprising SEQ ID NO:1. 
     
     
         10 . A kit for carrying out the method of  claim 7 , comprising reagents for the detection of a mutation in a protein sequence comprising SEQ ID NO:2. 
     
     
         11 . A method of detecting the presence or absence of Lafora's disease in a human comprising detecting a mutation in the nucleic acid sequence of  claim 1 , wherein the nucleic acid sequence comprises SEQ ID NO:1. 
     
     
         12 . A method of detecting the presence or absence of Lafora's disease in a human comprising detecting a mutation in the nucleic acid sequence of  claim 1 , wherein the nucleic acid sequence comprises:
 (a) a nucleic acid sequence comprising SEQ ID NO:1, wherein T can also be U;   (b) a nucleic acid sequence complementary to (a);   (c) a nucleic acid sequence that has substantial sequence homology to a nucleic acid sequence of (a) or (b);   (d) a nucleic acid sequence that is an analog of a nucleic acid sequence of (a), (b) or (c); or   (e) a nucleic acid sequence that hybridizes to a nucleic acid sequence of (a), (b), (c) or (d) under stringent hybridization conditions.   
     
     
         13 . A method for detecting the presence or absence of Lafora's disease comprising detecting a mutation in a protein according to  claim 6 . 
     
     
         14 . A method for diagnosing the presence of, or predisposition to, Lafora's disease in a human comprising:
 (a) obtaining a nucleic acid sample from the mammal;   (b) analyzing the nucleic acid sample to determine the presence of absence of a EPM2B gene mutation associated with Lafora's disease, wherein the presence of an EPM2B gene mutation associated with Lafora's disease indicates that the mammal is at risk for development of Lafora's disease.   
     
     
         15 . A method according to  claim 4 , wherein the mutation is a deletion, insertion, point mutation, or repeat sequence. 
     
     
         16 . A method according to  claim 14 , wherein the mutation is a deletion, insertion, point mutation, or repeat sequence.