A novel hepcidin mutation

Louis Praeger-Jahnsen, Karin Magnussen, Frank Vinholt Schiødt, Rikke Christina Therkildsen, Niels Jørgensen, Lennart Friis-Hansen*


Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


Background: The bioactive peptide hormone hepcidin-25 regulates iron levels by inhibiting iron transport to plasma via ferroportin. Hepcidin-25 is synthesized in the liver where the 84 amino acids pro-hepcidin is cleaved into the bioactive hepcidin-25. A patient admitted to the hospital presented with infertility and fatigue. Methods: Genomic DNA was purified from whole blood using the Maxwell 16 system (Promega). MLPA analysis was performed to detect large genomic rearrangements using the SALSA MLPA kit # P347, Hemochromatosis (MRC Holland, Holland). Plasma hepcidin measurements were performed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Results: A novel HAMP mutation (homozygous one base deletion in c.215delG, p.Cys72Serfs*?) was detected. The deletion in nucleotide 215 causes a frameshift altering the predicted protein sequence from cysteine13 in mature peptide. Whether this leads to nonsense mediated decay of the mRNA or synthesis of an aberrant peptide in unknown, but bioactive hepcidin-25 was undetectable in plasma. The patient had massive iron overload with ferritin up to 8360 µg/L. He was anaemic with a Hb at 7.0 mmol/L (11.3 g/dL) and suffered from hypogonadotropic hypogonadism with a total testosterone of 1.2 nmol/l. Continued treatment with venesection and gonadotropins led to reduced fatigue, reduction in iron overload, a normalized Hb and improvement of semen quality. Conclusion: A novel hepcidin mutation was detected in a patient with massive iron overload, fatigue and hypogonadotropic hypogonadism.

TidsskriftTransfusion Clinique et Biologique
Udgave nummer3
Sider (fra-til)335-340
StatusUdgivet - aug. 2023

Bibliografisk note

Funding Information:
Dick Nelson (Dept of Clinical Biochemistry, Helsingborg Hospital, Helsingborg, Sweden) is thanked for the hepcidin measurements.


Dyk ned i forskningsemnerne om 'A novel hepcidin mutation'. Sammen danner de et unikt fingeraftryk.