title: Homozygous deletion of HFE produces a phenotype similar to the HFE p.C282Y/p.C282Y genotype.
abstract: 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 homozygosity is often characterized by incomplete penetrance. Here, we describe the case of a woman who had a major structural alteration in the HFE gene. Molecular characterization revealed an Alu-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 common p.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.
authors.affiliation: Inserm U613, Brest, France. gerald.legac@univ-brest.fr
authors.forename: Gérald
authors.initials: G
authors.lastname: Le Gac
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gourlaouen
authors.forename: Christophe
authors.initials: C
authors.lastname: Ronsin
authors.forename: Vanna
authors.initials: V
authors.lastname: Géromel
authors.forename: Anne
authors.initials: A
authors.lastname: Bourgarit
authors.forename: Nathalie
authors.initials: N
authors.lastname: Parquet
authors.forename: Sylvia
authors.initials: S
authors.lastname: Quemener
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Maréchal
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Chen
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins