A novel hepcidin mutation

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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
JournalTransfusion Clinique et Biologique
Volume30
Issue number3
Pages (from-to)335-340
ISSN1246-7820
DOIs
Publication statusPublished - Aug 2023

Keywords

  • Haemochromatosis
  • Hepcidin
  • Hepcidin-mutation
  • Infertility
  • Iron overload
  • Humans
  • Semen Analysis
  • Iron Overload/genetics
  • Hypogonadism
  • Tandem Mass Spectrometry
  • Hepcidins
  • Chromatography, Liquid
  • Iron/metabolism
  • Mutation

Fingerprint

Dive into the research topics of 'A novel hepcidin mutation'. Together they form a unique fingerprint.

Cite this