title: Mutation analysis of the transferrin receptor-2 gene in patients with iron overload.
abstract: Three mutations in the transferrin receptor-2 gene have recently been identified in four Sicilian families with iron overload who had a normal hemochromatosis gene, HFE (C. Camaschella, personal communication). To determine the extent to which mutations in the transferrin receptor-2 gene occur in other populations with iron overload, we have completely sequenced this gene in 17 whites, 10 Asians, and 8 African Americans with iron overload and a C282C/C282C HFE genotype, as well as 4 subjects without iron overload and homozygous for the mutant HFE C282Y genotype, 5 patients with iron overload and homozygous for the mutant HFE C282Y genotype, and 5 normal individuals. None of the individuals exhibited the Sicilian mutations, Y250X in exon 6, M172K in exon 4, and E60X in exon 2. One iron-overloaded individual of Asian descent exhibited a I238M mutation which was subsequently found to be a polymorphism present in the Asian population at a frequency of 0.0192. The presence of the I238M mutation was not associated with an increase in ferritin or transferrin saturation levels. Three silent polymorphisms were also identified, nt 1770 (D590D) and nt 1851 (A617A) and a polymorphism at nt 2255 in the 3' UTR. Thus, mutations in the transferrin receptor-2 gene were not responsible for the iron overload seen in our subjects.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. plee@scripps.edu
authors.forename: P L
authors.initials: PL
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Halloran
authors.forename: C
authors.initials: C
authors.lastname: West
authors.forename: E
authors.initials: E
authors.lastname: Beutler
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D019190:Iron Overload / Q000209:etiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D017354:Point Mutation; D011110:Polymorphism, Genetic; D044469:Racial Groups / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human