Abstract
Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism and represents one of the most common inherited disorders in individuals of Northern European descent with an estimated carrier frequency between 1 in 8 and 1 in 10.1–3 In patients with HH, excessive iron deposition in a variety of organs leads to multiorgan dysfunction.4,5 The symptoms of HH are often similar to other diseases and for this reason, the diagnoses of HH is frequently not made until later in life. HH has commonly been identified with a combination of blood iron measurements and liver biopsy. It has been argued that early detection of the HH and a simple program of therapeutic phlebotomy would be of benefit in preventing the onset of this disease. With the advent of the gene cloning, it is now possible to detect HH with a DNA based test so that diagnosis can be made before the deleterious effects of excess iron are realized.
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References
Dadone, MM, Kushner, JP, Edwards, CQ, Bishop, DT, & Skolnick, MH, Hereditary Hemochromatosis analysis of laboratory expression of the disease by genotype in 18 pedigrees. Am. J. Clin. Pathol. 78, 196–207 (1982).
Edwards, CQ, et al. Prevalence of hemochromatosis among 11,065 presumably healthy donors. N. Engl. J. Med. 318, 1355–1362 (1988).
McLaren, CE, et al. Prevalence of heterozygotes for hemochromatosis in the white population of the United States. Blood 86, 2021–2027 (1995).
Bothwell, TH, Charlton, RW, & Motulsky, AG in The metabolic and molecular basis of inherited disease. (eds. Scriver, CR, Beaudet, AL, Sly, WS & Valle, D.) 2237–2269 (McGraw-Hill, New York. 1995).
Bacon, BR & Tavill, AS in Hepatology. A textbook of liver disease (eds. Zakim, D & Boyer, TD) 1439–1472 (WB Saunders, Philadelphia, 1996).
Feder, JN, et al. A novel MHC class 1-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13, 399–408 (1996).
Lauer, P, et al. Clone-Contig and STS maps of the hereditary hemochromatosis region on human chromosome 6p21.3-p22 Genome Research 7, 457–470 (1997).
Ruddy, DA, et al. A. 1.1-Mb transcript map of the hereditary hemochromatosis locus Genome Research 7, 441–456(1997).
Malissen, M, Malissen, B, & Jordan. BR. Exon/intron organization and complete nucleotide sequence of an HLA gene Proc. Natl. Acad. Sci. USA 79, 893–897 (1982).
Ting, JP & Baldwin, AS Regulaton of MHC gene expression Current Opinion in Immunology 5, 8–16 (1993).
Richardson, DR & Ponka, P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells Biochim. Biophys. Acta 1331, 1–40 (1997).
Gunshin, H, et al. Cloning and characterization of a mammalian proton-coupled metal-iron transporter 388, 482–488 (1997).
Lebron, JA, et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor Cell 93, 111–123 (1998).
Feder, JN, et al. The hemochromatosis founder mutation in HLA-H disrupts β2-microglobulin interaction and cell surface expression. J. Biol. Chem. 272; 14025–14028 (1997).
Parkkila, S, et al. Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract. Proc. Natl. Acad. Sci. USA 94, 2534–2539(1997).
Feder, JN, et al. The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding Proc. Natl. Acad. Sci. USA 95, 1472–1477 (1998).
Gross, CN, Irrinke, A, Feder, JN, & Enns, CA Co-trafficking of HFE with transferrin receptor implies role in intracellular iron regulation J. Biol. Chem. In press (1998).
McLaren, GD, Nathanson, MH, Jacobs, A, Trevett, D, & Thomson, W. Regulation of intestinal iron absroption and mucosal iron kinetics in hereditary hemochromatosis. J. lab. Clin. Med. 117, 390–401 (1991).
Banerjee, DB, Flanagan, PR, Cluett, J, & Valberg, LS. Transferrin receptors in the human gastrointestinal tract. Gastroenterology 91, 861–869 (1986).
Huebers, HA, Huebers, E, Csiba, E, Rummel, W, & Finch, CA. The significance of transferrin for intestinal iron absorption. Blood 61, 283–290. (1983).
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© 1999 Springer Science+Business Media New York
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Feder, J.N. et al. (1999). The Hereditary Hemochromatosis Gene and Iron Homeostasis. In: Abraham, N.G., Tabilio, A., Martelli, M., Asano, S., Donfrancesco, A. (eds) Molecular Biology of Hematopoiesis 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4797-6_43
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DOI: https://doi.org/10.1007/978-1-4615-4797-6_43
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