title: Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man.
abstract: The most common form of hemochromatosis is caused by mutations in the HFE gene. Rare forms of the disease are caused by mutations in other genes. We present a patient with hyperferritinemia and iron overload, and facial flushing. Magnetic resonance imaging was performed to measure hepatic iron overload, and a molecular study of the genes involved in iron metabolism was undertaken. The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and facial flushing improved after phlebotomy. Two of the patient's children were also studied, and the daughter was heterozygous for the mutation in the SLC40A1 gene, although she did not have hyperferritinemia. The patient presented a mild iron overload phenotype probably because of the two novel mutations in the HFE and SLC40A1 genes.
authors.affiliation: Unidad de Ferropatología, Departamento de Medicina Interna, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Del-Castillo-Rueda
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Moreno-Carralero
authors.forename: Luis-Antonio
authors.initials: LA
authors.lastname: Alvarez-Sala-Walther
authors.forename: Nuria
authors.initials: N
authors.lastname: Cuadrado-Grande
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; D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D013030:Spain; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D000098742:Ferroportin