Methods and kits for diagnosing and treating mental retardation

• US 20070015194A1
• Filed: 07/12/2006
• Published: 01/18/2007
• Est. Priority Date: 07/12/2005
• Status: Active Grant

• Current Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Original Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Inventors: Shohat, Mordechai, Basel, Lina
• Granted Patent: US 7,776,551 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

The present invention provides methods, kits, isolated nucleic acid sequences, antibodies and addressable oligonucleotides microarrays which can be for analyzing sequence alterations and detecting the expression level of CC2D1A or nup62 in cells of an individual and thus diagnose nonsyndromic mental retardation (NSMR) and/or infantile bilateral striatal necrosis (IBSN) in the individual. In addition, the present invention provides methods and pharmaceutical compositions which can be used to treat pathologies associated with mental retardation such as NSMR or IBS.

Claims

1. A method of diagnosing non-syndromic mental retardation (NSMR) in an individual, the method comprising analyzing a sequence of a CC2D1A of the individual, wherein an alteration in said sequence resulting in downregulation of an expression level and/or activity of said CC2D1A is indicative of the non-syndromic mental retardation, thereby diagnosing the non-syndromic mental retardation in the individual.

2. The method of claim 1, wherein said analyzing said sequence of said CC2D1A is effected by an isolated nucleic acid sequence capable of specifically hybridizing to a mutated CC2D1A and not to a wild-type CC2D1A nucleic acid sequence.

3. The method of claim 2, wherein said mutated CC2D1A nucleic acid sequence comprises a sequence alteration which results in downregulation of an expression level and/or activity of said CC2D1A.

4. The method of claim 1, wherein said alteration in said sequence is a deletion of nucleic acids 13891337-13894926 of a genomic sequence of said CC2D1A as set forth by GenBank Accession No. NC_—

000019.8.

5. The method of claim 2, wherein said isolated nucleic acid sequence is bound to a solid support.

6. The method of claim 2, wherein said isolated nucleic acid sequence is labeled.

7. The method of claim 1, wherein said analyzing said sequence of said CC2D1A is effected by an antibody which comprises an antigen recognition region capable of specifically binding to a mutated CC2D1A and not to a wild-type CC2D1A amino acid sequence.

8. The method of claim 7, wherein said mutated CC2D1A amino acid sequence comprises an amino acid sequence alteration which results in downregulation of an expression level and/or activity of said CC2D1A.

9. The method of claim 7, wherein said mutated CC2D1A is set forth by SEQ ID NO:

5.

10. The method of claim 7, wherein said antibody is bound to a solid support.

11. The method of claim 7, wherein the antibody is labeled.

12. A method of diagnosing non-syndromic mental retardation (NSMR) in an individual, the method comprising detecting an expression level of a CC2D1A of the individual, wherein a decrease in said expression level compared to said expression level of said CC2D1A of an unaffected individual is indicative of the non-syndromic mental retardation, thereby diagnosing the non-syndromic mental retardation in the individual.

13. The method of claim 12, wherein said detecting said expression level of said CC2D1A is effected by an isolated nucleic acid sequence capable of specifically hybridizing to a nucleic acid sequence of said CC2D1A.

14. The method of claim 12, wherein said isolated nucleic acid sequence is bound to a solid support.

15. The method of claim 12, wherein said isolated nucleic acid sequence is labeled.

16. The method of claim 12, wherein said detecting said expression level of said CC2D1A is effected by an antibody which comprises an antigen recognition region capable of specifically binding to an amino acid sequence of said CC2D1A.

17. The method of claim 16, wherein said antibody is bound to a solid support.

18. The method of claim 16, wherein the antibody is labeled.

19. An isolated nucleic acid sequence capable of specifically hybridizing to a mutated CC2D1A and not to a wild-type CC2D1A nucleic acid sequence.

20. An antibody comprising an antigen recognition region capable of specifically binding to a mutated CC2D1A and not to a wild-type CC2D1A amino acid sequence.

21. A kit for diagnosing non-syndromic mental retardation in an individual, the kit comprising a reagent for analyzing a sequence of a CC2D1A of the individual wherein an alteration in said sequence resulting in downregulation of an expression level and/or activity of said CC2D1A.

22. A kit for diagnosing non-syndromic mental retardation in an individual, the kit comprising a reagent for detecting an expression level of a CC2D1A of the individual wherein a decrease in said expression level compared to said expression level of said CC2D1A of an unaffected individual is indicative of the non-syndromic mental retardation.

23. A method of diagnosing infantile bilateral striatal necrosis (IBSN) in an individual, the method comprising analyzing a sequence of a nup62 of the individual, wherein an alteration in said sequence resulting in downregulation of an expression level and/or activity of said nup62 is indicative of the infantile bilateral striatal necrosis, thereby diagnosing the infantile bilateral striatal necrosis in the individual.

24. The method of claim 23, wherein said analyzing said sequence of said nup62 is effected by an isolated nucleic acid sequence capable of specifically hybridizing to a mutated nup62 and not to a wild-type nup62 nucleic acid sequence.

25. The method of claim 24, wherein said mutated nup62 nucleic acid sequence comprises a sequence alteration which results in downregulation of an expression level and/or activity of said nup62.

26. The method of claim 23, wherein said alteration in said sequence is a missense mutation 1429A→

C as set forth by SEQ ID NO;

68.

27. The method of claim 24, wherein said isolated nucleic acid sequence is bound to a solid support.

28. The method of claim 24, wherein said isolated nucleic acid sequence is labeled.

29. The method of claim 23, wherein said analyzing said sequence of said nup62 is effected by an antibody which comprises an antigen recognition region capable of specifically binding to a mutated nup62 and not to a wild-type nup62 amino acid sequence.

30. The method of claim 29, wherein said mutated nup62 amino acid sequence comprises an amino acid sequence alteration which results in downregulation of an expression level and/or activity of said nup62.

31. The method of claim 29, wherein said mutated nup62 comprises a proline residue at amino acid 391 as set forth by SEQ ID NO:

69.

32. The method of claim 29, wherein said antibody is bound to a solid support.

33. The method of claim 29, wherein the antibody is labeled.

34. A method of diagnosing infantile bilateral striatal necrosis (IBSN) in an individual, the method comprising detecting an expression level of a nup62 of the individual, wherein a decrease in said expression level compared to said expression level of said nup62 of an unaffected individual is indicative of the infantile bilateral striatal necrosis, thereby diagnosing the infantile bilateral striatal necrosis in the individual.

35. The method of claim 34, wherein said detecting said expression level of said nup62 is effected by an isolated nucleic acid sequence capable of specifically hybridizing to a nucleic acid sequence of said nup62.

36. The method of claim 35, wherein said isolated nucleic acid sequence is bound to a solid support.

37. The method of claim 35, wherein said isolated nucleic acid sequence is labeled.

38. The method of claim 34, wherein said detecting said expression level of said nup62 is effected by an antibody which comprises an antigen recognition region capable of specifically binding to an amino acid sequence of said nup62.

39. The method of claim 38, wherein said antibody is bound to a solid support.

40. The method of claim 38, wherein the antibody is labeled.

41. An isolated nucleic acid sequence capable of specifically hybridizing to a mutated nup62 and not to a wild-type nup62 nucleic acid sequence.

42. An antibody comprising an antigen recognition region capable of specifically binding to a mutated nup62 and not to a wild-type nup62 amino acid sequence.

43. A kit for diagnosing infantile bilateral striatal necrosis in an individual, the kit comprising a reagent for analyzing a sequence of a nup62 of the individual wherein an alteration in said sequence resulting in downregulation of an expression level and/or activity of said nup62.

44. A kit for diagnosing infantile bilateral striatal necrosis (IBSN) in an individual, the kit comprising a reagent for detecting an expression level of a nup62 of the individual wherein a decrease in said expression level compared to said expression level of said nup62 of an unaffected individual is indicative of the infantile bilateral striatal necrosis.

45. A method of diagnosing a pathology associated with mental retardation in an individual, the method comprising analyzing a sequence of a CC2D1A and/or nup62 of the individual, wherein an alteration in said sequence resulting in downregulation of an expression level and/or activity of said CC2D1A or said nup62 is indicative of the pathology associated with mental retardation, thereby diagnosing the pathology associated with mental retardation in the individual.

46. A method of diagnosing a pathology associated with mental retardation in an individual, the method comprising detecting an expression level of a CC2D1A and/or nup62 of the individual, wherein a decrease in said expression level compared to said expression level of said CC2D1A or said nup62 of an unaffected individual is indicative of the pathology associated with mental retardation, thereby diagnosing the pathology associated with mental retardation in the individual.

47. A method of treating a pathology associated with mental retardation, the method comprising upregulating in a cell of an individual in need thereof an activity of CC2D1A or nup62, thereby treating the pathology associated with mental retardation.