Ferroportin (FPN) mediates iron export from cells and this function is modulated 
by serum hepcidin. Mutations in the FPN gene (SLC40A1) lead to autosomal 
dominant iron overload diseases related either to loss or to gain of function, 
and usually characterized by normal or low transferrin saturation versus 
elevated transferrin saturation, respectively. However, for the same mutation, 
the phenotypic expression may vary from one patient to another. Using in vitro 
overexpression of wild-type or mutant FPN proteins, we characterized the 
functional impact of five recently identified FPN gene mutations regarding FPN 
localization, cell iron status, and hepcidin sensitivity. Our aim was to 
integrate functional results and biological findings in probands and relatives. 
We show that while the p.Arg371Gln (R371Q) mutation had no impact on studied 
parameters, the p.Trp158Leu (W158L), p.Arg88Gly (R88G), and p.Asn185Asp (N185D) 
mutations caused an iron export defect and were classified as loss-of-function 
mutations. The p.Gly204Ser (G204S) mutation induced a gain of FPN function. 
Functional studies are useful to determine whether or not a FPN gene mutation 
found in an iron overloaded patient is deleterious and to characterize its 
biological impact, especially when family studies are not fully informative 
and/or additional confounding factors may affect bio-clinical expression.