title: Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene.
abstract: Most hereditary hemochromatosis (HH) patients are homozygous for the C282Y mutation of the HFE gene. Nevertheless, penetrance of the disease is very variable. In some patients, penetrance can be mediated by concomitant mutations in other iron master genes. We evaluated the clinical impact of hepcidin (HAMP) and hemojuvelin mutations in a cohort of 100 Spanish patients homozygous for the C282Y mutation of the HFE gene. HAMP and hemojuvelin mutations were evaluated in all patients by bidirectional direct cycle sequencing. Phenotype-genotype interactions were evaluated. A heterozygous mutation of the HAMP gene (G71D) was found in only one out of 100 cases. Following, we performed a study of several members of that family, and we observed several members had a digenic inheritance of the C282Y mutation of the HFE gene and the G71D mutation of the HAMP gene. This mutation in the HAMP gene did not modify the phenotype of the individuals who were homozygous for the C282Y mutation. One other patient presented a new polymorphism in the hemojuvelin gene, without consequences in iron load or clinical course of the disease. In conclusion, HAMP and hemojuvelin mutations are rare among Spanish HH patients, and their impact in this population is not significant.
authors.affiliation: Hematology Department, Althaia Foundation, Flor de Lis 33, 08242, Manresa, Spain. aaltesh@althaia.cat
authors.forename: Albert
authors.initials: A
authors.lastname: Altès
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bach
authors.forename: Angels
authors.initials: A
authors.lastname: Ruiz
authors.forename: Anna
authors.initials: A
authors.lastname: Esteve
authors.forename: Jordi
authors.initials: J
authors.lastname: Felez
authors.forename: Angel F
authors.initials: AF
authors.lastname: Remacha
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Sardà
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins