Assays for Detecting WDR62 Mutations

Abstract

The present invention relates to compositions and methods for detecting mutations in WD repeat domain 62 (WDR62).

1 .- 11 . (canceled) 
     
     
         12 . A probe comprising a fragment of a WDR62 sequence or the complementary thereof, wherein the WDR62 sequence comprises a sequence selected from the group consisting of:
 (i) a sequence encoding (a) a serine at a position corresponding to position 224 of SEQ ID NO: 2, (b) a stop codon at a position corresponding to position 470 of SEQ ID NO:2, (c) a lysine at a position corresponding to position 526 of SEQ ID NO: 2, or (d) a stop codon at a position corresponding to position 526 of SEQ ID NO:2;   (ii) a 4 bp deletion corresponding to (TGCC) exon 31 beginning at a position corresponding to codon 1402 of the WDR62 coding region, leading to a premature stop codon at a position corresponding to codon 1413 of the WDR62 coding region (V1402GfsX12); and   (iii) a sequence corresponding to a 17-bp deletion in exon 30 leading to a frameshift at a position corresponding to codon 1280 of the WDR62 coding region resulting in a premature termination codon following a novel peptide of 20 amino acids (G1280AfxX21); and   wherein the probe hybridizes to a WDR62 nucleic acid, and wherein the probe is detectably labeled.   
     
     
         13 . The probe of  claim 12 , wherein the probe is an allele specific oligonucleotide probe. 
     
     
         14 . The probe of  claim 12 , wherein the probe is a perfect match probe. 
     
     
         15 . The probe of  claim 12 , wherein the probe specifically hybridizes to the WDR62 nucleic acid under stringent conditions. 
     
     
         16 . The probe of  claim 12 , wherein the probe has at least 15 nucleotides. 
     
     
         17 . The probe of  claim 12 , wherein the probe has at least 30 nucleotides. 
     
     
         18 . The probe of  claim 12 , wherein the probe has 10-50 nucleotides. 
     
     
         19 . The probe of  claim 12 , wherein the probe is 15-30 nucleotides. 
     
     
         20 . The probe of  claim 12 , wherein the nucleic acid probe is detectably labeled with a moiety selected from the group consisting of a luminescent label, a light scattering label, a radioactive label, and a fluorescent label. 
     
     
         21 . An array for detecting a mutation in at least one allele of WDR62, comprising a plurality of the probe of  claim 12 . 
     
     
         22 . A method of detecting a mutation in at least one allele of WDR62, comprising:
 (a) obtaining a test sample from a subject suspected of having a neurological disease or disorder, wherein the test sample comprises a WDR62 nucleic acid or a fragment thereof;   (b) contacting the test sample with a probe that hybridizes to a WDR62 sequence selected from the group consisting of:
 (i) a sequence encoding (a) a serine at a position corresponding to position 224 of SEQ ID NO: 2, (b) a stop codon at a position corresponding to position 470 of SEQ ID NO:2, (c) a lysine at a position corresponding to position 526 of SEQ ID NO: 2, or (d) a stop codon at a position corresponding to position 526 of SEQ NO:2; 
 (ii) a 4 bp deletion corresponding to (TGCC) in exon 31 beginning at a position corresponding to codon 1402 of the WDR62 coding region, leading to a premature stop codon at a position corresponding to codon 1413 of the WDR62 coding region (V1402GfsX12); 
 (iii) a sequence corresponding to a 17-bp deletion in exon 30 leading to a frameshift at a position corresponding to codon 1280 of the WDR62 coding region resulting in a premature termination codon following a novel peptide of 20 amino acids (G1280AfxX21); 
   (c) detecting hybridization of the nucleic acid probe to the WDR62 nucleic acid, wherein   
       hybridization is indicative of the presence of a mutation in the WDR62 nucleic acid in the test sample. 
     
     
         23 . The method of  claim 22 , wherein the subject is a human. 
     
     
         24 . The method of  claim 22 , wherein the subject is selected from the group consisting of a fetus, a child, an adolescent, and an adult. 
     
     
         25 . The method of  claim 22 , wherein the subject is a parent or a prospective parent. 
     
     
         26 . The method of  claim 22 , wherein the subject is suspected of being a carrier subject having at least one mutation in only one allele of WDR62. 
     
     
         27 . The method of  claim 22 , wherein the subject is suspected of being an affected subject having at least one mutation on each allele of WDR62. 
     
     
         28 . The method of  claim 22 , wherein the subject is suspected of having at least one neurological disease or disorder selected from the group consisting of intellectual disability, cerebral cortical malformation, microcephaly, agyria, pachygyria, hypoplasia of the corpus callosum, lissencephaly, schizencephaly, polymicrogyria and cerebellar hypoplasia. 
     
     
         29 . The method of  claim 22 , wherein the test sample from the subject comprises genomic DNA. 
     
     
         30 . The method of  claim 22 , wherein the test sample is a biological sample selected from the group consisting of blood, amniotic fluid, or cerebrospinal fluid.