title: Can defects in transferrin receptor 2 and hereditary hemochromatosis genes account for iron overload in HbH disease?
abstract: Iron overload was found to be the major cause of disability in Chinese HbH disease patients although they were not on regular blood transfusion. The transferrin receptor 2 (TFR2) and hereditary hemochromatosis (HFE) genes were examined to see if inheritance of these gene defects may be a possible cause of iron overload in 45 HbH patients. A novel intronic (IVS6 (+6) T-->A) mutation of the TFR2 gene was identified in one patient, and six others were found to carry a known missense mutation (exon 5, I238M) that was also present in one normal control subject. One HbH patient and one normal control carried the H63D mutation of the HFE gene. Since only eight out of 45 iron-overloaded HbH patients carry a defect in the TFR2 or HFE gene in the heterozygote state and their iron loading status was comparable to the matched controls without such defects, it would appear that the accumulation of excess iron in HbH disease is more likely a result of increase dietary absorption secondary to ineffective erythropoiesis.
authors.affiliation: University Department of Medicine, Queen Mary Hospital, Hong Kong, SAR China. vnychana@hkucc.hku.hk
authors.forename: Vivian
authors.initials: V
authors.lastname: Chan
authors.forename: Man Sim
authors.initials: MS
authors.lastname: Wong
authors.forename: Clara
authors.initials: C
authors.lastname: Ooi
authors.forename: F E
authors.initials: FE
authors.lastname: Chen
authors.forename: C S
authors.initials: CS
authors.lastname: Chim
authors.forename: R H S
authors.initials: RH
authors.lastname: Liang
authors.forename: D
authors.initials: D
authors.lastname: Todd
authors.forename: T K
authors.initials: TK
authors.lastname: Chan
mesh_terms: D000483:Alleles; D002681:China; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000209:etiology* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D011990:Receptors, Transferrin / Q000172:deficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017085:alpha-Thalassemia / Q000150:complications / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C503640:TFR2 protein, human