title: A novel HFE mutation (c.del478) results in nonsense-mediated decay of the mutant transcript in a hemochromatosis patient.
abstract: On admission to hospital Caucasian 61 year old male with jaundice was found to have unexplained increased serum iron indices. He had bilateral peripheral arthritis. On further investigation he had grade II hepatocellular iron staining and a hepatic index of 5.4 leading to a diagnosis of hereditary hemochromatosis. He lacked the common C282Y HFE mutation. We sequenced the complete HFE gene and found that he was heterozygous for a novel single nucleotide deletion (c.del478) in exon 3 of HFE. He lacks any other mutation in HFE or HJV, TFR2, HAMP and SLC40A1. The HFE mutation causes a frameshift (p.P160fs) that introduces a premature termination codon leading to mRNA degradation by nonsense-mediated decay. Haploinsufficiency of HFE may be one possible explanation for hemochromatosis in this patient.
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: Chun Yu
authors.initials: CY
authors.lastname: Lok
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Shearman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Suckling
authors.forename: Jacques
authors.initials: J
authors.lastname: Rochette
authors.forename: Alison T
authors.initials: AT
authors.lastname: Merryweather-Clarke
authors.forename: Kathryn J H
authors.initials: KJ
authors.lastname: Robson
mesh_terms: D018389:Codon, Nonsense / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020871:RNA Stability; D017384:Sequence Deletion; D014158:Transcription, Genetic
chemical_list: D018389:Codon, Nonsense; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins