Molecular and clinical correlates in iron overload associated with mutations in ferroportin.
Mutations in ferroportin (Fpn) result in iron overload. We correlate the behavior of three Fpn mutants in vitro with patients' phenotypes. Patients with Fpn mutations A77D or N174I showed macrophage iron loading. In cultured cells, FpnA77D did not reach the cell surface and cells did not export iron. Fpn mutant N174I showed plasma membrane and intracellular localization, and did not transport iron. Fpn mutation G80S was targeted to the cell surface and was transport competent, however patients showed macrophage iron. We suggest that FpnG80S represents a class of Fpn mutants whose behavior in vitro does not explain the patients' phenotype.
De Domenico
Ivana
I
Dipartimento di Scienze Microbiologiche Genetiche e Molecolari, Università di Messina, 98166 Messina, Italia.
McVey Ward
Diane
D
Nemeth
Elizabeta
E
Ganz
Tomas
T
Corradini
Elena
E
Ferrara
Francesca
F
Musci
Giovanni
G
Pietrangelo
Antonello
A
Kaplan
Jerry
J
D019943:Amino Acid Substitution; D027682:Cation Transport Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D006801:Humans; D019190:Iron Overload / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D000098742:Ferroportin
D027682:Cation Transport Proteins; D000098742:Ferroportin