Mecp2e1 gene

Abstract

The invention is a novel MECP2E1 splice variant and its corresponding polypeptide. The invention also includes methods of using these nucleic acid sequences and proteins in medical diagnosis and treatment of neuropsychiatric disorders or development disorders.

1 - 11 . (canceled) 
     
     
         12 . A method of preparing an MECP2 protein fraction from a subject useful for analyzing an MECP2E1 protein involved in neuropsychiatric or developmental disorder, comprising:
 (a) extracting proteins comprising an MECP2E1 protein from a sample from the subject;   (b) producing an MECP2E1 protein fraction of the proteins extracted in (a) by contacting the proteins extracted in (a) with antibodies or antibody fragments that bind to the MECP2E1 protein; and   (c) analyzing the MECP2E1 protein fraction produced in (b).   
     
     
         13 . The method of  claim 12 , wherein step (c) comprises detecting a mutation in a wild-type MECP2E1 protein, wherein the wild-type MECP2E1 protein has the amino acid sequence of SEQ ID NO: 4. 
     
     
         14 . The method of  claim 13 , wherein mutation is a premature truncation of the wild-type MECP2E1 protein. 
     
     
         15 . The method of  claim 14 , wherein the premature truncation occurs after amino acid at positions 36 or 97 of SEQ ID NO: 4. 
     
     
         16 . The method of  claim 12 , wherein the sample from the subject is a selected from blood, urine, serum, tears, saliva, and feces. 
     
     
         17 . The method of  claim 12 , wherein step (c) comprises performing a radioimmunoassay, enzyme immunoassay, immunofluorescence, immune-precipitation, latex agglutination, hemagglutination, or histochemical test. 
     
     
         18 . The method of  claim 17 , wherein the antibodies or antibody fragments of (b) are labeled with a detectable marker. 
     
     
         19 . The method of  claim 18 , wherein the detectable marker is an enzyme, fluorescent material, luminescent material, or radioactive material. 
     
     
         20 . The method of  claim 19 , wherein the enzyme is horseradish peroxidase, biotin, alkaline phosphatase, β-galactosidase, or acetylcholinesterase. 
     
     
         21 . The method of  claim 19 , wherein the fluorescent material is umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride, or phycoerythrin. 
     
     
         22 . The method of  claim 19 , wherein the luminescent material is luminol. 
     
     
         23 . The method of  claim 19 , wherein the radioactive material is S-35, Cu-64, Ga-67, Zr-89, Ru-97, Tc-99m, Rh-105, Pd-109, In-111, I-123, I-125, I-131, Re-186, Au-198, Au-199, Ph-203, At-211, Pb-212, or Bi-212. 
     
     
         24 . The method of  claim 12 , wherein step (c) comprises quantifying the amount of MECP2E1 protein in the sample. 
     
     
         25 . The method of  claim 12 , wherein the neuropsychiatric or developmental disorder is selected from autism, autism spectrum disorder, epilepsy, Angelman syndrome, Prader-Willi syndrome, encephalopathy, schizophrenia, bipolar affective disorder, depression, obsessive compulsive disorder, panic disorder, attention deficit hyperactivity disorder, ataxia, and mental retardation. 
     
     
         26 . A method of preparing an MECP2 amplified fraction from a subject useful for analyzing an MECP2E1 gene involved in neuropsychiatric or developmental disorder, comprising:
 (a) extracting nucleic acids comprising an MECP2E1 gene from a sample from the subject;   (b) producing an MECP2E1 amplified fraction of the nucleic acids extracted in (a) by contacting the nucleic acids extracted in (a) with primers to amplify the MECP2E1 gene, wherein the MECP2E1 amplified fraction comprises MECP2E1 amplified products; and   (c) analyzing the MECP2E1 amplified fraction produced in (b).   
     
     
         27 . The method of  claim 26 , wherein step (c) comprises detecting a mutation within exon 1, or in the intron-exon boundary immediately adjacent to exon 1, of a nucleic acid sequence encoding an MeCP2E1 protein having the amino acid sequence of SEQ ID NO: 4. 
     
     
         28 . The method of  claim 27 , wherein mutation is selected from the group consisting of:
 (1) a deletion of 11 consecutive base pairs in nucleotides 38 to 54 of SEQ ID NO: 1, the deletion causing a truncation of the MeCP2E1 protein of SEQ ID NO: 4 after amino acid 36;   (2) a deletion consisting of nucleotides 1-69 of exon 1 of SEQ ID NO: 1;   (3) an adenine to thymine change at nucleotide position 8 of SEQ ID NO: 1;   (4) a deletion of a T, G or TG between nucleotide positions 69-71 of SEQ ID NO: 1;   (5) a deletion of a T, G or TG between nucleotide positions 70-71 of SEQ ID NO: 1;   (6) a deletion of the nucleotide sequence GC at nucleotides −38 and −39 upstream of the position corresponding to nucleotide 1 of SEQ ID NO: 1;   (7) a deletion of the nucleotide sequence AG at nucleotides −19 and −20 upstream of the position corresponding to nucleotide 1 of SEQ ID NO:1;   (8) a deletion of 11 consecutive base pairs in nucleotides 38 to 54 of SEQ ID NO: 1, the deletion causing a truncation of the MeCP2E1 protein of SEQ ID NO: 4 after amino acid 36; and   (9) an adenine to thymine mutation at the nucleotide position corresponding to position 8 of SEQ ID NO: 1.   
     
     
         29 . A method of detecting Rett syndrome that is associated with a point mutation in the human MECP2 gene, comprising detecting the presence or absence of a point mutation which disrupts the initiation codon in exon 1 of a nucleic acid sequence encoding the MeCP2E1 protein having the amino acid sequence of SEQ ID NO.: 4 in a sample obtained from a human by (i) amplifying the sample nucleic acid sequence with primers that amplify an adenine to guanine change at nucleotide position 8 of SEQ ID NO:1 and comparing the amplified sample nucleic acid sequence to a control nucleic acid sequence or (ii) detecting with a probe an adenine to guanine change at nucleotide position 8 of SEQ ID NO:1, wherein the presence of the mutation in the sample nucleic acid sequence indicates that the human has Rett syndrome.