A novel HFE mutation (c.del478) results in nonsense-mediated decay of the mutant transcript in a hemochromatosis patient.
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.
Pointon
Jennifer J
JJ
Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Lok
Chun Yu
CY
Shearman
Jeremy D
JD
Suckling
Richard J
RJ
Rochette
Jacques
J
Merryweather-Clarke
Alison T
AT
Robson
Kathryn J H
KJ
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
D018389:Codon, Nonsense; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins