Homozygous deletion of HFE produces a phenotype similar to the HFE p.C282Y/p.C282Y genotype

摘要

Hemochromatosis is predominantly associated with the HFE p.C282Y homozygous genotype, which is carried by approximately 1 person in 200 in Northern European populations. However, p.C282Y ho-mozygosity is often characterized by incomplete penetrance. Here, we describe the case of a woman who had amajor structural alteration in the HFE gene. Molecular characterization revealed an 4/u-mediated recombination leading to the loss of the entire HFE gene sequence. Although homozygous for the HFE deleted allele, the woman had a phenotype similar to that seen in most women homozygous for the commonp.C282Y mutation. Contrasting with previously reported results in Hfe knockout and Hfe knockin mice, our report gives further evidence that progression of the disease depends on modifying factors.