Method of diagnosing schizophrenia by detecting a mutation in the (MTHFR) gene

• US 6,566,065 B1
• Filed: 06/12/2000
• Issued: 05/20/2003
• Est. Priority Date: 05/26/1994
• Status: Expired due to Term

• Current Assignee: McGill University
• Original Assignee: McGill University
• Inventors: Rozen, Rima
• Primary Examiner(s): Myers, Carla J.
• Application Number:
  US09/592,595
• Time in Patent Office: 1,072 Days
• Field of Search: 435/6, 435/91.2, 536/23.7, 536/24.31
• US Class Current: 435/6.13
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 9/0026 acting on CH-NH groups of donors (1.5)
• CPC Class Codes: C12N 9/0028 with NAD or NADP as acceptor (1.5.1)
• 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: C12Y 105/0102 Methylenetetrahydrofolate reductase [NAD(P)H] (1.5.1.20)

Abstract

The invention features methods for diagnosing subjects at risk for or suffering from a disease or disorder, such as a psychosis. Methods are also provided for selecting a preferred therapy for a particular subject or group of subjects.

Claims

1. A method of diagnosing a schizophrenia in a subject, said method comprising the steps of:

(a) analyzing the methylenetetrahydrofolate reductase (MTHFR) nucleic acid in a sample obtained from said subject; and

(b) determining the presence of a heterozygous C/T mutation at position 677 of MTHFR in said subject, wherein the presence of said mutation is indicative of said subject having said schizophrenia.

2. The method of claim 1, wherein said nucleic acid with said mutation encodes an MTHFR protein with reduced activity or reduced thermal stability.

3. A method of determining a risk for a schizophrenia or propensity thereto in a subject, said method comprising the steps of:

(a) analyzing the MTHFR nucleic acid in a sample obtained from said subject; and

(b) determining the presence of a heterozygous C/T mutation at position 677 of MTHFR in said subject, wherein the presence of said mutation is indicative of a risk for a schizophrenia or propensity thereto in said subject.

4. The method of claim 3, wherein said nucleic acid with said mutation encodes an MTHFR protein with reduced activity or reduced thermal stability.

5. The method of claim 3, wherein said nucleic acid further comprises an A/C mutation at position 1298.

6. A method of diagnosing a schizophrenia in a subject, said method comprising the steps of:

(a) analyzing the MTHFR nucleic acid in a sample obtained from said subject;

(b) determining the presence of a heterozygous C/T mutation at position 677 of MTHFR, wherein the presence of said mutation at position 677 is indicative of said subject having said schizophrenia; and

(c) determining the presence of at least one other MTHFR mutation at a position other than 677.

7. The method of claim 6, wherein the nucleic acid having said MTHFR mutation at position 677 and said MTHFR mutation at a position other than 677 encodes a protein having reduced activity or reduced thermal stability.

8. The method of claim 7, wherein the nucleic acid having said MTHFR mutation at a position other than 677 comprises at least one mutation selected from the group consisting of a G/A mutation at position 167, a G/A mutation at position 482, a C/T mutation a position 559, a C/T mutation at position 692, a C/T mutation at position 764, a G/A mutation at position 792+1, a C/T mutation at position 985, a C/T mutation at position 1015, a C/T mutation at position 1081, an A/C mutation at position 1298, and a T/C mutation at position 1317.

9. The method of claim 8, wherein the nucleic acid having said MTHFR mutation at a position other than 677 comprises an A/C mutation at position 1298.

10. A method of diagnosing a risk for a schizophrenia or propensity thereto in a subject, said method comprising the steps of:

(a) analyzing the MTHFR nucleic acid in a sample obtained from said subject;

(b) determining the presence of a heterozygous C/T mutation at position 677 of MTHFR, wherein the presence of said mutation at position 677 is indicative of a risk for a schizophrenia or propensity thereto; and

(c) determining the presence of at least one other MTHFR mutation at a position other than 677.

11. The method of claim 10, wherein the nucleic acid having said MTHFR mutation at position 677 and said MTHFR mutation at a position other than 677 encodes a protein having reduced activity or reduced thermal stability.

12. The method of claim 11, wherein the nucleic acid having said MTHFR mutation at a position other than 677 comprises at least one mutation selected from the group consisting of a G/A mutation at position 167, a G/A mutation at position 482, a C/T mutation a position 559, a C/T mutation at position 692, a C/T mutation at position 764, a G/A mutation at position 792+1, a C/T mutation at position 985, a C/T mutation at position 1015, a C/T mutation at position 1081, an A/C mutation at position 1298, and a T/C mutation at position 1317.

13. The method of claim 12, wherein the nucleic acid having said MTHFR mutation at a position other than 677 comprises an A/C mutation at position 1298.