Compositions and Methods for Diagnosing Autism

Abstract

Mutations located within the gene encoding the homeobox transcription factor, ENGRAILED 2 (EN2), have now been identified as molecular markers associated with susceptibility for autism and related disorders. Thus, the present invention relates to compositions in the form of diagnostic kits, primers and target sequences, for use in methods for determining the predisposition, the onset or the presence of autism spectrum disorder in a mammal. Moreover, therapeutic methods for treating a person inflicted with, or predisposed to, an autism spectrum disorder based upon modulating the level or activity of EN2 are also provided.

1 . A method for diagnosing the predisposition for developing autism spectrum disorder in a human comprising,
 obtaining a sample from a human subject, said sample comprising the ENGRAILED 2 intronic sequence of SEQ ID NO:11; and   detecting in said intronic sequence the presence of at least one single nucleotide polymorphism indicative of the predisposition for developing autism spectrum disorder.   
     
     
         2 . The method of  claim 1 , wherein the at least one single nucleotide polymorphism is:
 (i) an A at position 2236 of SEQ ID NO:11;   (ii) a C at position 2388 of SEQ ID NO:11; or   (iii) a combination of (i) and (ii).   
     
     
         3 . The method of  claim 2  (iii), further comprising a single nucleotide polymorphism selected from the group of rs3735652, rs6460013, rs7794177, rs3824068, rs2361688, rs3824067, ss38341503, rs3808332, rs3808331 and rs4717034. 
     
     
         4 . A diagnostic kit comprising one or more oligonucleotide primers hybridizable at or near a single nucleotide polymorphism in the ENGRAILED 2 intronic sequence of SEQ ID NO:11. 
     
     
         5 . The kit of  claim 4 , wherein said primers are labeled. 
     
     
         6 . The kit of  claim 4 , wherein the single nucleotide polymorphism is:
 (i) an A at position 2236 of SEQ ID NO:11;   (ii) a C at position 2388 of SEQ ID NO:11; or   (iii) a combination of (i) and (ii).   
     
     
         7 . The kit of  claim 6  (iii), further comprising a single nucleotide polymorphism selected from the group of rs3735652, rs6460013, rs7794177, rs3824068, rs2361688, rs3824067, ss38341503, rs3808332, rs3808331 and rs4717034. 
     
     
         8 . A method for identifying subjects most likely to respond to treatment for an autism spectrum disorder comprising
 obtaining a sample from a human subject, said sample comprising the ENGRAILED 2 intronic sequence of SEQ ID NO:11; and   detecting in said intronic sequence the presence of at least one single nucleotide polymorphism indicative of the predisposition for developing autism spectrum disorder, wherein the presence of the at least one single nucleotide polymorphism identifies said subject as most likely to respond to treatment for an autism spectrum disorder.   
     
     
         9 . The method of  claim 8 , wherein the at least one single nucleotide polymorphism is:
 (i) an A at position 2236 of SEQ ID NO:11;   (ii) a C at position 2388 of SEQ ID NO:11; or   (iii) a combination of (i) and (ii).   
     
     
         10 . The method of  claim 9  (iii), further comprising a single nucleotide polymorphism selected from the group of rs3735652, rs6460013, rs7794177, rs3824068, rs2361688, rs3824067, ss38341503, rs3808332, rs3808331 and rs4717034.