Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene

G. Montosi, A. Donovan, A. Totaro, C. Garuti, E. Pignatti, S. Cassanelli, C. C. Trenor, P. Gasparini, N. C. Andrews, A. Pietrangelo

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Abstract

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.

Original languageEnglish
Pages (from-to)619-623
Number of pages5
JournalJournal of Clinical Investigation
Volume108
Issue number4
DOIs
Publication statusPublished - 2001

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Iron
Missense Mutation
Mutation
Genes
MHC Class I Genes
Lod Score
Histocompatibility
Iron Overload
Hemochromatosis
Pedigree
Aspartic Acid
Alanine
metal transporting protein 1
Type 4 Hemochromatosis
Phenotype
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., ... Pietrangelo, A. (2001). Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. Journal of Clinical Investigation, 108(4), 619-623. https://doi.org/10.1172/JCI200113468

Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. / Montosi, G.; Donovan, A.; Totaro, A.; Garuti, C.; Pignatti, E.; Cassanelli, S.; Trenor, C. C.; Gasparini, P.; Andrews, N. C.; Pietrangelo, A.

In: Journal of Clinical Investigation, Vol. 108, No. 4, 2001, p. 619-623.

Research output: Contribution to journalArticle

Montosi, G, Donovan, A, Totaro, A, Garuti, C, Pignatti, E, Cassanelli, S, Trenor, CC, Gasparini, P, Andrews, NC & Pietrangelo, A 2001, 'Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene', Journal of Clinical Investigation, vol. 108, no. 4, pp. 619-623. https://doi.org/10.1172/JCI200113468
Montosi, G. ; Donovan, A. ; Totaro, A. ; Garuti, C. ; Pignatti, E. ; Cassanelli, S. ; Trenor, C. C. ; Gasparini, P. ; Andrews, N. C. ; Pietrangelo, A. / Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 4. pp. 619-623.
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