Diagnosis of Hereditary Spastic Paraplegias (HSP) by Identification of a Mutation in the ZFYVE26 Gene or Protein

Abstract

The Invention relates to an ex vivo method of diagnosing or predicting a hereditary spastic paraplegias (HSP), in a subject, which method comprises detecting a mutation in the ZFYVE26 gene or protein (spastizin), wherein said mutation is indicative of a hereditary spastic paraplegias (HSP).

1 - 15 . (canceled) 
     
     
         16 . An oligonucleotide specifically hybridizes to a region of ZFYVE26 gene sequence that contains a mutation, wherein the mutation is:
 (i) a substitution mutation selected from the group consisting of c.307G>T, c.427G>T, c.1240G>T, c.1477C>T, c.2182C>T, c.4312C>T, c.5422C>T, c.5791-6G>A/r.5791_5792ins5791-4_5791-1, c.5485-1G>A, c.7128+2T>A/r.6987_7128del, c.6011G>C;   (ii) a deletion selected from the group consisting of c.2049de1T, c.4068_4069delTG, c.5036delT, c.6702_6771del;   (iii) an insertion selected from the group consisting of c.2331_2332insA and c.6296_6297insT; or   (iv) a complex rearrangement which is g.67316025_67319414del/g.67316025_67316026insTCTA/g.67319319_67319414i nv;   wherein the nucleic acid position corresponds to SEQ ID NO:1, and   
       wherein the nucleic acid is detectably labeled. 
     
     
         17 . The oligonucleotide of  claim 16 , wherein the oligonucleotide has at least 10 nucleotides. 
     
     
         18 . The oligonucleotide of  claim 16 , wherein the oligonucleotide has at least 15 nucleotides. 
     
     
         19 . The oligonucleotide of  claim 16 , wherein the oligonucleotide has at least 20 nucleotides. 
     
     
         20 . The oligonucleotide of  claim 16 , wherein the oligonucleotide has 10-100 nucleotides. 
     
     
         21 . The oligonucleotide of  claim 16 , wherein the oligonucleotide has 10-70 nucleotides. 
     
     
         22 . The oligonucleotide of  claim 16 , wherein the oligonucleotide is detectably labeled with a radiolabel, a fluorescent label, an enzymatic labels, or a sequence tag. 
     
     
         23 . The oligonucleotide of  claim 16 , wherein the hybridization is under a high stringent condition. 
     
     
         24 . A kit comprising at least one oligonucleotide of  claim 16 . 
     
     
         25 . The kit of  claim 24 , further comprising a hybridization reagent. 
     
     
         26 . The kit of  claim 25 , further comprising sequence determination reagents and sequence determination primers. 
     
     
         27 . A method of detecting a mutation in a ZFYVE26 nucleic acid comprising:
 (a) contacting a ZFYVE26 nucleic acid in a sample with a detectably labeled oligonucleotide that specifically hybridizes to a region of the ZFYVE26 nucleic acid containing a mutation, wherein said mutation is
 (i) a substitution mutation selected from the group consisting of c.307G>T, c.427G>T, c.1240G>T, c.1477C>T, c.2182C>T, c.4312C>T, c.5422C>T, c.5791 - 6G>A/r.5791_5792ins5791-4_5791-1, c.5485-1G>A, c.7128+2T>A/r.6987_7128del, c.6011G>C; 
 (ii) a deletion selected from the group consisting of c.2049delT, c.4068_4069deITG, c.5036delT, c.6702_6771del; 
 (iii) an insertion selected from the group consisting of c.2331_2332insA and c.6296_6297insT; or 
 (iv) a complex rearrangement which is g.67316025_67319414del/g.67316025_67316026 insTCTA/g.67319319_67319414inv; 
   (b) detecting hybridization of the oligonucleotide to the ZFYVE26 nucleic acid, wherein hybridization is indicative of the presence of the mutation in a ZFYVE26 nucleic acid.