Analysis of the HFE gene in a large Spanish kindred with hereditary hemochromatosis

BACKGROUND: Hereditary hemochromatosis (HH) is an inborn error of iron meta bolism that is inherited as an autosomal recessive trait. Recently, it has been shown that the HFE gene, located telomeric to HLA-A on chromosome 6 is mutated in most patients with HH. Moreover, the phenotypic expression of h ereditary hemochromatosis is influenced by sex and environmental agents suc h as alcohol and dietary iron intake. SUBJECTS AND METHOD: We have studied 40 subjects from a family some of whic h members have HH. DNA was obtained from nucleated peripheral blood cells, and exons 2 and 4 and intron 5 of the HFE gene were amplified by PCR and di gested with specific restriction enzymes. RESULTS: Analysis of the HFE gene revealed that 29 members of the family ca rry some of the three HFE mutations (C282Y, H63D and S65C). Nevertheless, o nly those homozygous for the C282Y mutation develop HH. In this family, the allele 187G of exon 2 mutation is cosegregated with the allele IVS5-47 A i n intron 5. CONCLUSIONS: Analysis of the HFE gene in the members of a large Spanish kin dred, living in the same geographical area, shows that only those homozygou s for the C282Y mutation develop hemochromatosis.