Ferroportin diseases: functional studies, a link between genetic and clinical phenotype.

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.

A novel N491S mutation in the human SLC11A2 gene impairs protein trafficking and in association with the G212V mutation leads to microcytic anemia and liver iron overload.

Background: DMT1 is a transmembrane iron transporter involved in iron duodenal absorption and cellular iron uptake. Mutations in the human SLC11A2 gene coding DMT1 lead to microcytic anemia and hepatic iron overload, with unexpectedly low levels of plasma ferritin in the presence of iron stores.

Design And Methods: We report a patient with a similar phenotype due to two mutations in the SLC11A2 gene, the known p.

Sex and acquired cofactors determine phenotypes of ferroportin disease.

Background & Aims: Ferroportin disease is characterized by iron overload. It has an autosomal-dominant pattern of inheritance and has been associated with mutations in the SLC40A1 gene, which encodes the cellular iron exporter ferroportin. Since the first description in 2001, about 30 mutations have been reported; the heterogeneity of ferroportin disease phenotypes has led to the hypothesis that the nature of the mutation affects the function of the protein in different ways.

Molecular diagnosis of genetic iron-overload disorders.

Genetic iron overload has long been confined to the picture of classical hemochromatosis related to the HFE C282Y mutation (type 1 hemochromatosis). C282Y homozygosity affects approximately three people out of 1000 of the Caucasian population, representing one of the most frequent genetic predispositions. It has, however, rapidly become clear that the HFE C282Y mutation is not the sole culprit in genetic iron overload.

A new mutation in the hepcidin promoter impairs its BMP response and contributes to a severe phenotype in HFE related hemochromatosis.

Low levels of hepcidin are responsible for the development of iron overload in p.Cys282Tyr HFE related hemochromatosis. Every genetic factor lowering the hepcidin gene expression could contribute to a more severe phenotype in HFE hemochromatosis.

A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload.

Background: Elevated serum ferritin levels are frequently encountered in clinical situations and once iron overload or inflammation has been ruled out, many cases remain unexplained. Genetic causes of hyperferritinemia associated to early cataract include mutations in the iron responsive element in the 5' untranslated region of the L ferritin mRNA, responsible for the hereditary hyperferritinemia cataract syndrome.

Design And Methods: We studied 91 probands with hyperferritinemia comprising 25 family cases belonging to families with at least two cases of unexplained hyperferritinemia, and 66 isolated cases.

Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway modulate HFE hemochromatosis penetrance.

Most cases of genetic hemochromatosis (GH) are associated with the HFE C282Y/C282Y (p.Cys282Tyr/p.Cys282Tyr) genotype in white populations.

[Pathophysiology and genetics of classic HFE (type 1) hemochromatosis].

Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene (C282Y mutation). The p.