Autosomal-dominant hemochrom-atosis is associated with a mutation in the ferroportin (SLC11A3) gene
Open accessAbstract
Hemochromatosis is a progressive iron overload disorder that is prevalent among individuals of European descent.It is usually inherited in an autosomal-recessive pattern and associated with missense mutations in HFE, an atypical major histocompatibility class I gene.Recently, we described a large family with autosomal-dominant hemochromatosis not linked to HFE and distinguished by early iron accumulation in reticuloendothelial cells.Through analysis of a large pedigree, we have determined that this disease maps to 2q32.The gene encoding ferroportin (SLC11A3), a transmembrane iron export protein, lies within a candidate interval defined by highly significant lod scores.We show that the iron-loading phenotype in autosomal-dominant hemochromatosis is associated with a nonconservative missense mutation in the ferroportin gene.This missense mutation, converting alanine to aspartic acid at residue 77 (A77D), was not seen in samples from 100 unaffected control individuals.We propose that partial loss of ferroportin function leads to an imbalance in iron distribution and a consequent increase in tissue iron accumulation.
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Hemochromatosis can result from mutations in the gene encoding ferroportin, the target of hepcidin activity.
“Hemochromatosis can also result from mutations in the gene encoding ferroportin, the target of hepcidin activity.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [156]
Binding of ferritin L to the cell surface of liver, T-, and B-lymphoid cells was demonstrated.
“binding of ferritin L to the cell surface of liver, T-, and B-lymphoid cells was demonstrated (7, 208)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [208]
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- Authors
- Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., & Pietrangelo, A.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- IRCCS Materno Infantile Burlo Garofolo (IT)
- Corresponding author
- Pietrangelo, Antonello
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2001-08-15
- Volume
- 108
- Issue
- 4
- Pages
- 619-623
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC209405
- OpenAlex
- W2105923433
- Cited by
- 557
- References
- 18
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 14 · 2020: 10 · 2019: 5 · 2018: 16 · 2017: 18 · 2016: 16 · 2015: 16 · 2014: 14 · 2013: 20 · 2012: 19
- FWCI
- 25.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- ferroportin, missense mutations, iron overload, HFE gene, reticuloendothelial cells, gene mapping
- MeSH terms
- Hemochromatosis Protein, Ferroportin, Animals, Carrier Proteins, Chromosomes, Human, Pair 2, Codon, Exons, Female, Genes, Dominant, Hemochromatosis, HLA Antigens, Homeostasis, Humans, Iron, Italy, Lod Score, Male, Membrane Proteins, Pedigree, Phenotype, Receptors, Transferrin, Mononuclear Phagocyte System, Histocompatibility Antigens Class I, Genetic Heterogeneity, Iron Overload, Amino Acid Substitution, Mutation, Missense, Cation Transport Proteins, Mice
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