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 - 14 . (canceled) 
     
     
         15 . 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).   
     
     
         16 . The method of  claim 15 , 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. 
     
     
         17 . The method of  claim 16 , 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.   
     
     
         18 . The method of  claim 15 , wherein the sample from the subject is a selected from blood, urine, serum, tears, saliva, and feces. 
     
     
         19 . The method of  claim 15 , wherein step (c) comprises sequencing the MECP2 amplified products. 
     
     
         20 . The method of  claim 15 , wherein step (b) comprises PCR, rtPCR, multiplex ligation-dependent probe amplification (MLPA), ligase chain reaction, or NASBA. 
     
     
         21 . The method of  claim 15 , 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. 
     
     
         22 . A method of detecting a mutation in the human MECP2 gene, comprising: (a) contacting an MECP2 nucleic acid in a human sample with a labeled oligonucleotide that hybridizes under stringent conditions to the sequence portion within the MECP2 nucleic acid comprising the mutation; and (b) detecting the hybridization of the labeled oligonucleotide with the MECP2 nucleic acid under stringent hybridization conditions, wherein detection of hybridization indicates that the mutation is present in the MECP2 nucleic acid; wherein the mutation is selected from the group consisting of: (i) a deletion of the nucleotide sequence GC at nucleotides −38 and −39 upstream of a position corresponding to nucleotide 1 of SEQ ID NO. 1; and (ii) a deletion of the nucleotide sequence AG at nucleotides −19 and −20 upstream of a position corresponding to nucleotide 1 of SEQ ID NO. 1. 
     
     
         23 . A method of detecting the presence of a mutation or deletion in a nucleic acid molecule encoding the MeCP2E1 protein comprising: a) analyzing a test sample containing a nucleic acid sequence encoding the MeCP2E1 protein consisting of SEQ ID NO.: 4 for a mutation or deletion within exon 1, or in the intron-exon boundary immediately adjacent to exon 1, of the nucleic acid sequence; and b) comparing the results of the analysis of the test sample with the results of analysis of a control sample, wherein the control sample comprises the nucleic acid encoding the MeCP2E1 protein consisting of SEQ ID NO.: 4 without a mutation or deletion within exon 1, or in the intron-exon boundary immediately adjacent to exon 1.