title: A novel Y231del mutation of HFE in hereditary haemochromatosis provides in vivo evidence that the Huh-7 is a human haemochromatotic cell line.
abstract: Hereditary haemochromatosis (HH), which is mainly associated with a C282Y polymorphism in HFE, is common among Caucasians of north European descent, but is very rare among Asians. Herein, we report a 43-year-old Japanese man who was diagnosed as having HH. A laboratory examination revealed an elevated serum iron level (280 μg/dl), hyperferritinemia (1698 ng/ml) and a low serum level of hepcidin-25 (4.0 ng/ml). Abdominal magnetic resonance imaging revealed findings suggestive of iron accumulation in the liver and pancreas. HFE gene sequencing in the patient revealed a novel homozygous TAC nucleotide deletion (c. 691_693del) responsible for the loss of a tyrosine at position 231 (p. Y231del) of the HFE protein. This homozygous Y231del mutation was recently found in the Huh-7 hepatoma cell line and was shown to prevent the translocation of HFE to the cell surface. This clinical case provides in vivo evidence suggesting that Huh-7 is undoubtedly a human haemochromatotic cell line and, as such, is a valuable tool for investigating the pathogenesis of HFE-related HH in humans.
authors.affiliation: Saiseikai Takaoka Hospital, Takaoka, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takano
authors.forename: Hideki
authors.initials: H
authors.lastname: Niimi
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Atarashi
authors.forename: Takuro
authors.initials: T
authors.lastname: Sawasaki
authors.forename: Teiichi
authors.initials: T
authors.lastname: Terasaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakabayashi
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Terumi
authors.initials: T
authors.lastname: Takahara
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D001483:Base Sequence; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D018962:Phlebotomy; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*; D053719:Tandem Mass Spectrometry
chemical_list: D023181:Antimicrobial Cationic Peptides; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C545475:hepcidin 25, human