title: A novel mutation in the SLC40A1 gene associated with reduced iron export in vitro.
abstract: Ferroportin disease is an inherited disorder of iron metabolism and is caused by mutations in the ferroportin gene (SLC40A1). We present a patient with hyperferritinemia, iron overload in the liver with reticuloendothelial distribution and also in the spleen, and under treatment with erythropheresis. A molecular study of the genes involved in iron metabolism (HFE, HJV, HAMP, TFR2, SLC40A1) was undertaken. In vitro functional studies of the novel mutation found in the SLC40A1 gene was performed. The patient was heterozygous for a novel mutation, c.386T>C (p.L129P) in the SLC40A1 gene; some of his relatives were also heterozygous for this mutation. In vitro functional studies of the L129P mutation on ferroportin showed it impairs its capacity to export iron from cells but does not alter its sensitivity to hepcidin. These findings and the iron overload phenotype of the patient suggest that the novel mutation c.386T>C (p.L129P) in the SLC40A1 gene has incomplete penetrance and causes the classical form of ferroportin disease.
authors.affiliation: Centro de Investigación, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Moreno-Carralero
authors.forename: Juan-Antonio
authors.initials: JA
authors.lastname: Muñoz-Muñoz
authors.forename: Nuria
authors.initials: N
authors.lastname: Cuadrado-Grande
authors.forename: Rafaela
authors.initials: R
authors.lastname: López-Rodríguez
authors.forename: María
authors.initials: M
authors.lastname: José Hernández-Alfaro
authors.forename: Alejandro
authors.initials: A
authors.lastname: del-Castillo-Rueda
authors.forename: Rafael
authors.initials: R
authors.lastname: Enríquez-de-Salamanca
authors.forename: Manuel
authors.initials: M
authors.lastname: Méndez
authors.forename: María-Josefa
authors.initials: MJ
authors.lastname: Morán-Jiménez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005293:Ferritins / Q000097:blood; D005838:Genotype; D057809:HEK293 Cells; D064451:Hepcidins / Q000008:administration & dosage; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D064451:Hepcidins; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron