Identification of a novel mutation in the HAMP gene that causes non-detectable hepcidin molecules in a Japanese male patient with juvenile hemochromatosis.
Hepcidin is an iron-regulatory hepatic peptide hormone encoded by the HAMP gene that downregulates iron export from enterocytes and macrophages into the blood plasma. In this study, we identified a novel mutation in the HAMP gene of a 58-year-old Japanese male patient with hemochromatosis. By direct sequencing of the five hereditary hemochromatosis-related genes, HFE, HAMP, HJV, TFR2, and SLC40A1, the previously unreported p.R75X mutation was identified, and the patient was found to be homozygous for the mutation. No other potentially pathogenic mutations were detected. In an LC-MS/MS analysis, hepcidin molecules were not detected in the patient's serum or urine. These results indicate that the p.R75X mutation causes iron overload by impairing the hepcidin system.
Department of Medical Technology, Nagoya University Graduate School of Health Sciences, Nagoya 461-8673, Japan. ai-hat@dpc.agu.ac.jp
Ai
A
Hattori
Naohisa
N
Tomosugi
Yasuaki
Y
Tatsumi
Ayami
A
Suzuki
Kazuhiko
K
Hayashi
Yoshiaki
Y
Katano
Yasutaka
Y
Inagaki
Tetsuya
T
Ishikawa
Hisao
H
Hayashi
Hidemi
H
Goto
Shinya
S
Wakusawa
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000235:genetics* / Q000652:urine; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D006432:Hemochromatosis / Q000097:blood / Q000151:congenital* / Q000235:genetics / Q000652:urine; D064451:Hepcidins; D006720:Homozygote; D006801:Humans; D007564:Japan; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins