title: Hereditary hemochromatosis should be considered a conformational disorder.
abstract: Hereditary hemochromatosis (HH) is a genetic disease associated with iron overload, in which individuals homozygous for the mutant C282Y HFE associated allele are at risk of developing liver disease, diabetes and arthritis. Conformational diseases are a class of disorders associated with the expression of misfolded protein and examples include conditions such as Alzheimer's, Parkinson's, Z alpha 1-antitrypsin deficiency and Huntington's diseases. HFE C282Y is a mutant protein that does not fold correctly forming aggregates and is retained in the Endoplasmic Reticulum (ER). Consequently, we propose that HH associated with the C282Y HFE mutation should be considered a conformational disorder.
authors: Hepatology Research Division, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St James Hospital, Dublin 8, Ireland. mlawles@tcd.ie
authors: Matthew W
authors: MW
authors: Lawless
authors: Arun K
authors: AK
authors: Mankan
authors: Suzanne
authors: S
authors: Norris
mesh_terms: D000483:Alleles; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008957:Models, Genetic; D008962:Models, Theoretical; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D012306:Risk
chemical_list: D004220:Disulfides; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D003545:Cysteine