title: HLA-H and associated proteins in patients with hemochromatosis.
abstract: BACKGROUND
  The 845A(C282Y) mutation in the HLA-H gene accounts for most cases of hereditary hemochromatosis in patients who are of European origin. Some lack this mutation, however, and it is not present in Asian patients. Thus, other mutations either in HLA-H or associated proteins may be present in such patients. HLA-H associates with beta-2-microglobulin. Calreticulin associates with class 1 HLA proteins and appears to be identical with mobilferrin, a putative iron transport protein. These two proteins are therefore candidates for mutations in patients with hemochromatosis.
  
  
  METHODS
  We have sequenced the coding region and parts of introns of the HLA-H gene, the beta-2-microglobulin gene, and the calreticulin (mobilferrin) gene of 10, 7, and 5 hemochromatosis patients, respectively, selecting those who were not homozygous for the 845A(C282Y) mutation. The number of chromosomes at risk studied were 18 for HLA-H, 14 for beta-2-microglobulin and 10 for calreticulin.
  
  
  RESULTS
  We detected 3 new intronic polymorphisms in the HLA-H gene, each a point mutation. Some differences from published sequences of beta-2-microglobulin and calreticulin were documented, but these were uniformly present in all samples.
  
  
  CONCLUSIONS
  The lack of additional mutations in the HLA-H gene is remarkable, and we speculate that the C282Y mutation may be a gain-of-function change.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA. beutler@scripps.edu
authors.forename: E
authors.initials: E
authors.lastname: Beutler
authors.forename: C
authors.initials: C
authors.lastname: West
authors.forename: T
authors.initials: T
authors.lastname: Gelbart
mesh_terms: D001208:Asia / Q000208:ethnology; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D037282:Calreticulin; D017931:DNA Primers; D005060:Europe / Q000208:ethnology; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000209:etiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007438:Introns; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012261:Ribonucleoproteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D001613:beta 2-Microglobulin / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D037282:Calreticulin; D017931:DNA Primers; C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012261:Ribonucleoproteins; D001613:beta 2-Microglobulin