title: Sex and acquired cofactors determine phenotypes of ferroportin disease.
abstract: OBJECTIVE
  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. We studied genotypes and phenotypes of a large cohort of patients with ferroportin disease.
  
  
  METHODS
  We studied clinical, biochemical, imaging, histologic, and genetic data from 70 affected subjects from 33 families with 19 mutations.
  
  
  RESULTS
  We found that ferroportin disease, at the time of diagnosis, has limited consequences in the absence of cofactors. Data indicated that transferrin saturation, which correlated with fibrosis and levels of alanine aminotransferase, might be a marker of disease severity. Although the study was performed in a large number of families, we observed incomplete penetrance and no correlation between genotypes and phenotypes.
  
  
  CONCLUSIONS
  Members of families with ferroportin disease should be screened for biochemical parameters of iron metabolism as well as genotype to detect silent mutations that might cause disease with acquired or genetic cofactors. Patients should be followed up long term to identify potential complications of the disease.
authors.affiliation: Service des Maladies du Foie, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin and INSERM U-991, University Hospital Pontchaillou, Rennes, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Lan
authors.forename: Annick
authors.initials: A
authors.lastname: Mosser
authors.forename: Martine
authors.initials: M
authors.lastname: Ropert
authors.forename: Lénaïck
authors.initials: L
authors.lastname: Detivaud
authors.forename: Véronique
authors.initials: V
authors.lastname: Loustaud-Ratti
authors.forename: Denis
authors.initials: D
authors.lastname: Vital-Durand
authors.forename: Laurent
authors.initials: L
authors.lastname: Roget
authors.forename: Edouard
authors.initials: E
authors.lastname: Bardou-Jacquet
authors.forename: Bruno
authors.initials: B
authors.lastname: Turlin
authors.forename: Véronique
authors.initials: V
authors.lastname: David
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
authors.forename: Yves
authors.initials: Y
authors.lastname: Deugnier
authors.forename: Pierre
authors.initials: P
authors.lastname: Brissot
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Jouanolle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011990:Receptors, Transferrin / Q000235:genetics; D012720:Severity of Illness Index; D012727:Sex Characteristics; D014168:Transferrin / Q000378:metabolism; D055815:Young Adult; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D058851:GPI-Linked Proteins; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D014168:Transferrin; D000098742:Ferroportin