title: A novel homozygous frameshift deletion c.471del of HFE associated with hemochromatosis.
abstract: A 47-year-old white male patient who manifested biochemical evidence of iron overload was found not to be a carrier of the three most common mutations, C282Y, H63D and S65C, of the HFE gene. Sequencing of the patient's entire HFE-coding region revealed a presence of a previously undescribed frameshift deletion c.471del in exon 3 resulting in a premature termination of a nonsense HFE protein. Interestingly, the patient was a homozygous carrier of this novel mutation and his hemochromatosis phenotype can be explained by the fact that he has no intact HFE protein. To the best of our knowledge, this is the first description of a complete loss of function of the HFE gene because of a homozygous mutation. The patient's son was found to be a heterozygous carrier of the mutation and has so far exhibited no indications of iron overload. Similarly, A*02-B*40/A*02-B*40 homozygous human leukocyte antigen (HLA) genotype was determined in the patient and heterozygous A*02-B*40/A*03-B*35 HLA genotype in his son. Thus, the novel HFE frameshift deletion c.471del was linked to the HLA-A*02-B*40 haplotype.
authors.affiliation: Blood Transfusion Centre of Slovenia, Slajmerjeva 6, SI-1000 Ljubljana, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Cukjati
authors.forename: S
authors.initials: S
authors.lastname: Koren
authors.forename: V
authors.initials: V
authors.lastname: Curin Serbec
authors.forename: B
authors.initials: B
authors.lastname: Vidan-Jeras
authors.forename: R
authors.initials: R
authors.lastname: Rupreht
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006432:Hemochromatosis / Q000235:genetics* / Q000276:immunology; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins