Genetic haemochromatosis: genes and mutations associated with iron loading

Abstract

Haemochromatosis is an autosomal recessive disorder common among Caucasians that leads to iron overload. Molecular studies have shown that the disease is prevalently due to a mutation in the HFE gene. Although C282Y in the homozygous state remains the most common patient's genotype, other genes and genetic mutations are associated with haemochromatosis. Haemochromatosis type 2, a severe form with juvenile onset, is due to mutations in an unidentified gene on chromosome 1q. Haemochromatosis type 3 is linked to a locus on 7q22 and is due to mutations in the transferrin receptor 2. Haemochromatosis type 4, the only autosomal dominant form, is caused by mutations in ferroportin 1 on 2q32. The genes responsible for African and neonatal forms of iron overload are still unknown. The identification of all of the genes associated with haemochromatosis is critical for molecular-based diagnosis and central to our understanding of the regulation of iron homeostasis.