title: Spectrum and haplotypes of the HFE hemochromatosis gene in Iran: H63D in beta-thalassemia major and the first E277K homozygous.
abstract: We present the molecular analysis of HFE gene in 400 Southwest Iranian individuals. We have studied 43 newborn, selected for the presence of HbBart's at birth, 203 normal adult and 154 transfused patients affected with beta-thalassemia. Mutation analysis consisted of amplification and direct sequencing using two different pairs of forward and reverse primers. The C282Y and S65C mutations were not found. The H63D mutation was present with an allele frequency of 0.10 in newborns, 0.082 in normal adults and 0.080 in the beta-thalassemia major populations, respectively. No differences were found between normal adults and thalassemia major patients suggesting that this mutation does not increase mortality in beta-thalassemia. The H63D mutation was found associated with haplotype VI in 41% of the chromosomes. Other haplotypes were found suggesting a multicentric origin rather than a single mutation of European origin. While sequencing exon 4, a G --> A transition was found in the proximity of the C282Y mutation. The effect of this single base substitution (E277K) previously reported in an Asian individual and now found in homozygous form in a young transfused and chelated homozygous beta-thalassemia patient is not yet known.
authors.affiliation: Hemostasis and thrombosis Unit, Hematology Research Center, School of Medicine, University of Medical Sciences, Shiraz, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Karimi
authors.forename: Majid
authors.initials: M
authors.lastname: Yavarian
authors.forename: Paola
authors.initials: P
authors.lastname: Delbini
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Shirin
authors.initials: S
authors.lastname: Farjadian
authors.forename: Gemino
authors.initials: G
authors.lastname: Fiorelli
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000293:Adolescent; D000328:Adult; D020029:Base Pairing; D002648:Child; D002875:Chromosomes / Q000235:genetics; D004252:DNA Mutational Analysis; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D006455:Hemoglobins, Abnormal / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007492:Iran; D008565:Membrane Proteins / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D011110:Polymorphism, Genetic; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D006455:Hemoglobins, Abnormal; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; C030448:hemoglobin Bart's