title: Identification of new mutations of hepcidin and hemojuvelin in patients with HFE C282Y allele.
abstract: HFE-hemochromatosis is the most common form of hereditary hemochromatosis. The disorder is associated with the homozygous C282Y mutation and has variable phenotype, being modulated by environmental and genetic factors. Candidate modifier genes are hemojuvelin and hepcidin, which are responsible for juvenile hemochromatosis. We used DHPLC to scan mutations in these genes in a cohort of unrelated patients with C282Y mutation. They consisted of 136 C282Y homozygous, 43 heterozygous, and 42 C282Y/H63D compound heterozygous, plus 62 controls subjects. Mutations and polymorphisms were found in 16 patients and 4 controls. Abnormally high indices of iron status were found in subjects C282Y/H63D heterozygous for the N196K hemojuvelin mutation and the -72C > T hepcidin substitution. The already described G71D mutation of hepcidin did not induce evident modification of the C282Y/H63D phenotype. The data show that heterozygous mutations of the hemojuvelin gene contribute like those of hepcidin to the phenotypic heterogeneity of hemochromatosis. However, they are rare and explain only a minor portion of the variable penetrance of the disorder.
authors.affiliation: Dipartimento Materno Infantile e Tecnologie Biomediche, Università di Brescia, A.O. Spedali Civili, Brescia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Biasiotto
authors.forename: Antonella
authors.initials: A
authors.lastname: Roetto
authors.forename: Filomena
authors.initials: F
authors.lastname: Daraio
authors.forename: Anna
authors.initials: A
authors.lastname: Polotti
authors.forename: Gian Mario
authors.initials: GM
authors.lastname: Gerardi
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Laura
authors.initials: L
authors.lastname: Cremonesi
authors.forename: Paolo
authors.initials: P
authors.lastname: Arosio
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
mesh_terms: D000483:Alleles; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*
chemical_list: D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C103673:HFE protein, human; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins