Journal ArticleDOI
Genetics of Hemochromatosis
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TLDR
The role of HFE in the process of normal iron metabolism has yet to be clearly defined and Mechanisms by which C282Y and H63D may disrupt the normal functioning of H FE have been suggested.Abstract:
Hereditary hemochromatosis (HHC) is a common autosomal recessive disorder of iron metabolism that results in progressive iron overload and can be fatal if untreated The hemochromatosis gene (HFE) was identified by positional cloning in 1996 Two missense mutations have been described in HFE The majority of HHC patients are homozygous for a cysteine-to-tyrosine substitution (C282Y); however, a small number are homozygous for a histidine-to-aspartic-acid substitution (H63D) or are heterozygous for both of these mutations Mechanisms by which C282Y and H63D may disrupt the normal functioning of HFE have been suggested, but the role of HFE in the process of normal iron metabolism has yet to be clearly definedread more
Citations
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Journal ArticleDOI
Comparison of the Interactions of Transferrin Receptor and Transferrin Receptor 2 with Transferrin and the Hereditary Hemochromatosis Protein HFE
Anthony P. West,Melanie J. Bennett,Vera M. Sellers,Nancy C. Andrews,Caroline A. Enns,Pamela J. Bjorkman +5 more
TL;DR: The results imply that HFE regulates Tf-mediated iron uptake only from the classical TfR and that TFR2 does not compete for HFE binding in cells expressing both forms of T fR.
Journal ArticleDOI
Genes that modify the hemochromatosis phenotype in mice
TL;DR: The results suggest that each of these genes might be a candidate modifier of the human hemochromatosis phenotype, with insight into the pathogenesis of HH.
Journal ArticleDOI
Iron Metabolism: Iron Deficiency and Iron Overload
TL;DR: This review discusses inherited iron deficiency and iron overload disorders and recent insights into their pathophysiology.
Journal ArticleDOI
Hemochromatosis: Genetics and Pathophysiology
TL;DR: Hepcidin, with its cognate receptor, ferroportin, has emerged as a central regulator of iron homeostasis; all of the known causes of hemochromatosis appear to prevent this system from functioning normally.
Journal ArticleDOI
HFE and Transferrin Directly Compete for Transferrin Receptor in Solution and at the Cell Surface
TL;DR: Binding studies using a heterodimeric form of soluble T fR demonstrate that TfR does not exhibit cooperativity in heterotropic ligand binding, suggesting that some or all of the effects of HFE on iron homeostasis result from competition with Fe-Tf for Tf R binding.
References
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Journal ArticleDOI
A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis
John N. Feder,Andreas Gnirke,Winston Thomas,Zenta Tsuchihashi,David A. Ruddy,A. Basava,F. Dormishian,R. Domingo,Michael C. Ellis,A. Fullan,L.M. Hinton,Norman Jones,B.E. Kimmel,Gregory S. Kronmal,Peter M. San Francisco Lauer,V.K. Lee,Deborah B. Loeb,Felipa A. Mapa,Erin E. McClelland,Nicole C. Meyer,Gabe Mintier,N. Moeller,T. E. Moore,E. Morikang,Cynthia E. Prass,Leah Quintana,Steven M. Starnes,Randall C. Schatzman,K.J. Brunke,Dennis Drayna,Neil Risch,Bruce R. Bacon,Roger K. Wolff +32 more
TL;DR: Using linkage-disequilibrium and full haplotype analysis, this paper identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes.
Journal Article
A novel MHC class-I-like gene is mutated in patients with hereditary haemochromatosis
TL;DR: Using linkage–disequilibrium and full haplotype analysis, a region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical–by–descent in 85% of patient chromosomes is identified, containing a gene related to the MHC class I family, termed HLA–H, containing two missense alterations.
Journal ArticleDOI
The Cellular Basis of Hepatic Fibrosis -- Mechanisms and Treatment Strategies
TL;DR: Advances in the isolation and characterization of liver cells, in conjunction with progress in matrix and cytokine biology, have led to important new insights about the cellular basis of hepatic fibrosis, including the hepatic lipocyte.
Journal ArticleDOI
Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis.
Claus Niederau,Rudolf Fischer,A. Sonnenberg,Wolfgang Stremmel,Hans J. Trampisch,Georg Strohmeyer +5 more
TL;DR: It is concluded that patients with hemochromatosis diagnosed in the precirrhotic stage and treated by venesection have a normal life expectancy, whereas cirrhotic patients have a shortened life expectancy and a high risk of liver cancer even when complete iron depletion has been achieved.
Journal ArticleDOI
The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding
John N. Feder,David Penny,Alivelu Irrinki,Vince K. Lee,José A. Lebrón,Nicole Watson,Zenta Tsuchihashi,Elliott Sigal,Pamela J. Bjorkman,Randall C. Schatzman +9 more
TL;DR: A molecular link between HFE and a key protein involved in iron transport, the TfR, is established and the possibility that alterations in this regulatory mechanism may play a role in the pathogenesis of hereditary hemochromatosis is raised.
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A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis
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