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.