Identification of a novel mutation in the HAMP gene that causes non-detectable hepcidin molecules in a Japanese male patient with juvenile hemochromatosis.

Abstract

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.

• Authors: Ai Hattori, Naohisa Tomosugi, Yasuaki Tatsumi, Ayami Suzuki, Kazuhiko Hayashi, Yoshiaki Katano, Yasutaka Inagaki, Tetsuya Ishikawa, Hisao Hayashi, Hidemi Goto, Shinya Wakusawa
• Journal: Blood cells, molecules & diseases (Blood Cells Mol Dis) Vol. 48 Issue 3 Pg. 179-82 (Mar 15 2012) ISSN: 1096-0961 [Electronic] United States
• PMID: 22297252 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antimicrobial Cationic Peptides
• HAMP protein, human
• Hepcidins

Topics

• Amino Acid Sequence
• Antimicrobial Cationic Peptides (blood, genetics, urine)
• Asian People (genetics)
• Base Sequence
• Hemochromatosis (blood, congenital, genetics, urine)
• Hepcidins
• Homozygote
• Humans
• Japan
• Liver (metabolism, pathology)
• Male
• Middle Aged
• Mutation