Methods of diagnosing hypophosphatemic disorders

• US 8,586,317 B2
• Filed: 04/11/2011
• Issued: 11/19/2013
• Est. Priority Date: 07/19/2000
• Status: Expired due to Term

• Current Assignee: ADVANCED RESEARCH & TECHNOLOGY INSTITUTE, Ludwig-Maximilians-Universitat Munchen Abeteilung Mediziniche Genetik
• Original Assignee: ADVANCED RESEARCH & TECHNOLOGY INSTITUTE, Ludwig-Maximilians-Universitat Munchen Abeteilung Mediziniche Genetik
• Inventors: Econs, Michael, Strom, Tim Matthias, Meitinger, Thomas, White, Kenneth E.
• Primary Examiner(s): Saoud, Christine J
• Application Number:
  US13/084,203
• Publication Number:
  US 20120064544A1
• Time in Patent Office: 953 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• 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 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: C07K 14/50 Fibroblast growth factor [FGF]
• 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
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

The present invention relates to methods of diagnosing hypophosphatemic disorders.

Claims

1. A method of diagnosing a hypophosphatemic disorder in a mammal, said method comprising (a) obtaining a biological sample from said mammal and (b) contacting said biological sample with a reagent that detects the level of fibroblast growth factor-23 (FGF23) polypeptide in said sample,

wherein the FGF23 polypeptide is a polypeptide selected from the group consisting of a polypeptide comprising the amino acid sequence of SEQ ID NO:

2, a polypeptide comprising the amino acid sequence of SEQ ID NO;

4, a polypeptide comprising an arginine-to-glutamine mutation at amino acid 176 (R176Q) relative to SEQ ID NO;

2, a polypeptide comprising an arginine-to-glutamine mutation at amino acid 179 (R179Q) relative to SEQ ID NO;

2, and a polypeptide comprising an arginine-to-tryptophan mutation at amino acid 179 (R179W) relative to SEQ ID NO;

2,

wherein an elevated level of FGF23 polypeptide in said sample, relative to the level of FGF23 polypeptide in a sample obtained from a control mammal, is an indication that said mammal is afflicted with said hypophosphatemic disorder, thereby diagnosing said hypophosphatemic disorder in said mammal.

2. The method of claim 1, wherein said mammal afflicted with said hypophosphatemic disorder is afflicted with one of the hypophosphatemic disorders selected from the group consisting of X-linked hereditary rickets (XLH), hereditary hypophosphatemic rickets (HHRH), hypophosphatemic bone disease (HBD), autosomal dominant hypophosphatemic rickets (ADHR), tumor induced osteomalacia, epidermal nevus syndrome, fibrous dysplasia, and nephrolithiasis.

3. The method of claim 1, wherein said biological sample is selected from the group consisting of blood and urine.

4. The method of claim 1, wherein said reagent is an FGF23 antibody.

5. The method of claim 1, wherein said reagent is detectably labeled.

6. The method of claim 1, wherein said reagent is detectably labeled with a label selected from the group consisting of a radioisotope, a bioluminescent compound, a chemiluminescent compound, a fluorescent compound, a metal chelate, and an enzyme.