A novel HFE mutation (c.del478) results in nonsense-mediated decay of the mutant transcript in a hemochromatosis patient

作者：Pointon Jennifer J; Lok Chun Yu; Shearman Jeremy D; Suckling Richard J; Rochette Jacques; Merryweather Clarke Alison T; Robson Kathryn J H^*

来源：Blood Cells, Molecules, and Diseases, 2009, 43(2): 194-198.

DOI：10.1016/j.bcmd.2009.04.007

• Hemochromatosis
• HFE
• c.del478
• Nonsense-mediated decay
• Haploinsufficiency

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 11 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.

• 出版日期2009-10