Mutations associated with iron disorders

Abstract

The invention features a method of diagnosing an iron disorder, e.g., hemochromatosis, or a genetic susceptibility to developing such a disorder in a mammal by determining the presence of a mutation in exon 2 or in an intron of an HFE nucleic acid.

1 . A method of diagnosing an iron disorder or a genetic susceptibility to developing said disorder in a mammal, comprising determining the presence of a mutation in exon 2 of an HFE nucleic acid in a biological sample from said mammal, wherein said mutation is not a C→G substitution at nucleotide 187 of SEQ ID NO: 1 and wherein the presence of said mutation is indicative of said disorder or a genetic susceptibility to developing said disorder.  
     
     
         2 . The method of  claim 1 , wherein said disorder is hemochromatosis.  
     
     
         3 . The method of  claim 1 , wherein said nucleic acid is a DNA molecule.  
     
     
         4 . The method of  claim 1 , wherein said nucleic acid is a RNA molecule.  
     
     
         5 . The method of  claim 1 , wherein said mutation is a missense mutation at nucleotide 314 of SEQ ID NO:1.  
     
     
         6 . The method of  claim 5 , wherein said mutation is 314C.  
     
     
         7 . The method of  claim 6 , wherein said mutation results in expression of mutant HFE gene product I105T.  
     
     
         8 . The method of  claim 1 , wherein said mutation is at nucleotide 277 of SEQ ID NO:1.  
     
     
         9 . The method of  claim 8 , wherein said mutation is 277C.  
     
     
         10 . The method of  claim 9 , wherein said mutation results in expression of mutant HFE gene product G93R.  
     
     
         11 . The method of  claim 1 , wherein said mutation is at nucleotide 193 of SEQ ID NO:1.  
     
     
         12 . The method of  claim 11 , wherein said mutation is 193T.  
     
     
         13 . The method of  claim 12 , wherein said mutation results in expression of mutant HFE gene product S65C.  
     
     
         14 . The method of  claim 1 , wherein said biological sample is selected from the group consisting of whole blood, cord blood, serum, saliva, plasma, effusions, ascites, urine, stool, buccal tissue, liver tissue, kidney tissue, cerebrospinal fluid, skin, hair and tears.  
     
     
         15 . The method of  claim 1 , wherein said mammal is a human.  
     
     
         16 . A kit for diagnosing an iron disorder or a genetic susceptibility to developing said disorder in a mammal, comprising an antibody which preferentially binds to an epitope of a mutant HFE gene product, wherein said gene product comprises amino acid substitution I105T, G93R, or S65C.  
     
     
         17 . A kit for diagnosing an iron disorder or a genetic susceptibility to developing said disorder in a mammal, comprising an antibody which preferentially binds to an epitope of a wild type HFE gene product, wherein said gene product comprises amino acid substitution I105, G93, or S65.