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.

We claim: 
     
         1 . A method of detecting a developmental disorder associated with a mutation or deletion in a MECP2E1 gene comprising detecting the presence or absence of a non-inactivating mutation or deletion in, or upstream of, exon 1 of a nucleic acid sequence encoding a MeCP2E1 protein having the amino acid sequence of SEQ ID No.: 4 in a sample from a human, wherein the presence of a non-inactivating mutation or deletion in or upstream of exon 1 of said nucleic acid sequence indicates that the human has a neuropsychiatric disorder or developmental disorder. 
     
     
         2 . The method according to  claim 1  comprising:
 (a) amplifying the nucleic acid sequences in the sample with primers X1F (5′-CCATCACAGCCAATGACG-3′) (SEQ ID No. 19) and X1R (5′-AGGGGGAGGGTAGAGAGGAG-3′) (SEQ ID No. 20) in a polymerase chain reaction; 
 (b) amplifying the nucleic acid sequences from a control with the same primers; 
 (c) sequencing the amplified sequences; and 
 (d) comparing the sample sequences to the control sequences, 
 
       wherein a difference or deletion of nucleotides in the sample sequence compared to the control sequence indicates that the human has a developmental disorder. 
     
     
         3 . The method according to  claim 1  comprising performing multiplex ligation-dependent probe amplification in all four exons of the MECP2E1 gene sequence of SEQ ID No.: 1. 
     
     
         4 . The method according to  claim 1  wherein the developmental disorder is mental retardation. 
     
     
         5 . The method according to  claim 1  wherein the mutation or deletion is selected from the group consisting of: 1) an insertion of one or more copies of the trinucleotide sequence GCC between nucleotides 11 and 29 of SEQ ID No.: 1; (2) a deletion of one or more copies of the trinucleotide sequence GCC between nucleotides 11 and 29 of SEQ ID No.: 1; (3) an insertion of the nucleotide sequence GGA between nucleotides 38 and 54 of SEQ ID No.:1; (4) a deletion of the nucleotide sequence GC at nucleotides −38 and -39 upstream of nucleotide 1 of SEQ ID No.: 1; and (5) a deletion of the nucleotide sequence AG at nucleotides −19 and -20 upstream of nucleotide 1 of SEQ ID No.: 1. 
     
     
         6 . A method of detecting a developmental disorder associated with a mutation or deletion in a MECP2E1 gene in a human comprising:
 (a) obtaining a nucleic acid sample from said human; and   (b) detecting the presence or absence of a mutation or deletion in or upstream of exon 1 of a nucleic acid sequence encoding the amino acid sequence of SEQ ID No.: 4,   
       wherein the presence of a mutation or deletion in or upstream of exon 1 of said nucleic acid sequence indicates that the human has a developmental disorder. 
     
     
         7 . The method according to  claim 6  wherein the disorder is mental retardation. 
     
     
         8 . The method of  claim 6  wherein the nucleic acid sequence comprises SEQ ID No.: 1. 
     
     
         9 . The method according to  claim 8  wherein the presence or absence of a mutation or deletion in or upstream of exon 1 in the MECP2E1 transcript of a MECP2 gene comprising SEQ ID No.: 1, wherein the MECP2E1 transcript comprises SEQ ID NO: 3, is detected by performing multiplex ligation-dependent probe amplification in all four exons of the MECP2 gene sequence of SEQ ID No.: 1. 
     
     
         10 . The method according to  claim 8  wherein the disorder is mental retardation. 
     
     
         11 . The method according to  claim 10  the mutation or deletion being detected is selected from the group consisting of: 1) an insertion of one or more of the trinucleotide sequence GCC between nucleotides 11 and 29 of SEQ ID No.: 1; (2) a deletion of one or more copies of the trinucleotide sequence GCC between nucleotides 11 and 29 of SEQ ID No.: 1; (3) an insertion of the nucleotide sequence GGA between nucleotides 38 and 54 of SEQ ID No.: 1; (4) a deletion of the nucleotide sequence GC at nucleotides-38 and -39 upstream of nucleotide 1 of SEQ ID No.: 1; and (5) a deletion of the nucleotide sequence AG at nucleotides −19 and -20 upstream of nucleotide 1 of SEQ ID No.: 1. 
     
     
         12 . A method of detecting the presence or absence of a mutation or deletion in a nucleic acid molecule encoding a MeCP2E1 protein comprising:
 (a) analyzing a test sample containing a nucleic acid encoding a MeCP2E1 protein comprising SEQ ID No.: 4 for a mutation or deletion in or upstream of exon 1 of said 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 a MeCP2E1 protein of SEQ ID No.: 4 without a mutation or deletion in or upstream of exon 1; and wherein a difference in, or deletion of, nucleotides in the sample sequence from the control sequence indicates a mutation or deletion in the test sample nucleic acid.   
     
     
         13 . The method of  claim 12  wherein the nucleic acid sequence comprises SEQ ID NO.: 1. 
     
     
         14 . The method according to  claim 13  wherein the mutation or deletion being detected in or upstream of exon 1 of SEQ ID No.: 1 is selected from the group consisting of: 1) an insertion of one or more of the trinucleotide sequence GCC between nucleotides 11 and 29 of SEQ ID No.: 1; (2) a deletion of one or more copies of the trinucleotide sequence GCC between nucleotides 11 and 29 of SEQ ID No.: 1; (3) an insertion of the nucleotide sequence GGA between nucleotides 38 and 54 of SEQ ID No.: 1; (4) a deletion of the nucleotide sequence GC at nucleotides-38 and -39 upstream of nucleotide 1 of SEQ ID No.: 1; and (5) a deletion of the nucleotide sequence AG at nucleotides −19 and -20 upstream of nucleotide 1 of SEQ ID No.: 1.