Hereditary hemochromatosis should be considered a conformational disorder.
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.
Lawless
Matthew W
MW
Hepatology Research Division, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St James Hospital, Dublin 8, Ireland. mlawles@tcd.ie
Mankan
Arun K
AK
Norris
Suzanne
S
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
D004220:Disulfides; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D003545:Cysteine