{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:21:29Z","timestamp":1791973289041,"version":"4.3.4"},"reference-count":86,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr\/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp) should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and\/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.<\/jats:p>","DOI":"10.3390\/ijms13021497","type":"journal-article","created":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T12:23:15Z","timestamp":1328098995000},"page":"1497-1511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Paulo C. J. L.","family":"Santos","sequence":"first","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Krieger","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/GIM.0b013e31819d30f2","article-title":"HFE-associated hereditary hemochromatosis","volume":"11","author":"Alexander","year":"2009","journal-title":"Genet. Med"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1053\/gast.2001.21913","article-title":"Hemochromatosis: Diagnosis and management","volume":"120","author":"Bacon","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.cca.2011.04.007","article-title":"Hereditary hemochromatosis: Laboratory evaluation","volume":"412","author":"Moyer","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1002\/hep.23879","article-title":"A phase 1\/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis","volume":"52","author":"Phatak","year":"2010","journal-title":"Hepatology"},{"key":"ref_5","first-page":"1506","article-title":"HJV hemochromatosis, iron overload, and hypogonadism in a Brazilian man: Treatment with phlebotomy and deferasirox","volume":"13","author":"Santos","year":"2012","journal-title":"Int. J. Mol. Sci"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dupradeau, F.Y., Pissard, S., Coulhon, M.P., Cadet, E., Foulon, K., Fourcade, C., Goossens, M., Case, D.A., and Rochette, J (2008). An unusual case of hemochromatosis due to a new compound heterozygosity in HFE (p.[Gly43Asp;His63Asp]+[Cys282Tyr]): Structural implications with respect to binding with transferrin receptor 1. Hum. Mutat, 29.","DOI":"10.1002\/humu.9517"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00277-008-0572-y","article-title":"Non-classical hereditary hemochromatosis in Portugal: Novel mutations identified in iron metabolism-related genes","volume":"88","author":"Mendes","year":"2009","journal-title":"Ann. Hematol"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1136\/gut.2005.078063","article-title":"Molecular insights into the pathogenesis of hereditary haemochromatosis","volume":"55","author":"Pietrangelo","year":"2006","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1373\/clinchem.2006.068684","article-title":"Hereditary hemochromatosis: Genetic complexity and new diagnostic approaches","volume":"52","author":"Swinkels","year":"2006","journal-title":"Clin. Chem"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1136\/jmg.34.4.275","article-title":"Global prevalence of putative haemochromatosis mutations","volume":"34","author":"Pointon","year":"1997","journal-title":"J. Med. Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000243791","article-title":"The role of hepcidin in iron metabolism","volume":"122","author":"Nemeth","year":"2009","journal-title":"Acta Haematol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1590\/S0100-879X2009007500031","article-title":"HFE gene mutations and iron status of Brazilian blood donors","volume":"43","author":"Santos","year":"2010","journal-title":"Braz. J. Med. Biol. Res"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1365-3148.2009.00944.x","article-title":"Iron deficiency and frequency of HFE C282Y gene mutation in Brazilian blood donors","volume":"19","author":"Terada","year":"2009","journal-title":"Transfus. Med"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1182\/blood-2009-01-199109","article-title":"Iron overload in the Asian community","volume":"114","author":"Lok","year":"2009","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.bcmd.2011.02.008","article-title":"Hereditary hemochromatosis: Mutations in genes involved in iron homeostasis in Brazilian patients","volume":"46","author":"Santos","year":"2010","journal-title":"Blood Cells Mol. Dis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12185-010-0760-0","article-title":"The molecular basis of iron overload disorders and iron-linked anemias","volume":"93","author":"Kaplan","year":"2011","journal-title":"Int. J. Hematol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev.pathol.4.110807.092205","article-title":"Regulation of hepcidin and iron-overload disease","volume":"4","author":"Lee","year":"2009","journal-title":"Annu. Rev. Pathol"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1053\/j.gastro.2010.06.013","article-title":"Hereditary hemochromatosis: Pathogenesis, diagnosis, and treatment","volume":"139","author":"Pietrangelo","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jhep.2010.08.004","article-title":"Hepcidin in human iron disorders: Therapeutic implications","volume":"54","author":"Pietrangelo","year":"2011","journal-title":"J. Hepatol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1006\/mgme.2000.3037","article-title":"Nonexpressing homozygotes for C282Y hemochromatosis: Minority or majority of cases?","volume":"71","author":"Adams","year":"2000","journal-title":"Mol. Genet. Metab"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00277-004-0966-4","article-title":"Analysis of HFE gene mutations (C282Y, H63D, and S65C) in the Ecuadorian population","volume":"84","author":"Leone","year":"2005","journal-title":"Ann. Hematol"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.bcmd.2005.06.012","article-title":"Unique genetic profile of hereditary hemochromatosis in Russians: High frequency of C282Y mutation in population, but not in patients","volume":"35","author":"Potekhina","year":"2005","journal-title":"Blood Cells Mol. Dis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.bcmd.2010.08.008","article-title":"HFE gene mutations in patients with primary iron overload: Is there a significant improvement in molecular diagnosis yield with HFE sequencing?","volume":"45","author":"Santos","year":"2010","journal-title":"Blood Cells Mol. Dis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1440-1746.2004.03262.x","article-title":"Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease patients in India","volume":"19","author":"Thakur","year":"2004","journal-title":"J. Gastroenterol. Hepatol"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pelucchi, S., Mariani, R., Bertola, F., Arosio, C., and Piperno, A (2009). Homozygous deletion of HFE: The Sardinian hemochromatosis. Blood, 113.","DOI":"10.1182\/blood-2008-12-196493"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/47417","article-title":"Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor","volume":"403","author":"Bennett","year":"2000","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1006\/bcmd.2002.0575","article-title":"Decreased liver hepcidin expression in the Hfe knockout mouse","volume":"29","author":"Ahmad","year":"2002","journal-title":"Blood Cells Mol. Dis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0140-6736(03)12602-5","article-title":"Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis","volume":"361","author":"Bridle","year":"2003","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1399-0004.2005.00413.x","article-title":"HJV gene mutations in European patients with juvenile hemochromatosis","volume":"67","author":"Gehrke","year":"2005","journal-title":"Clin. Genet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1053\/j.gastro.2009.06.057","article-title":"Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis","volume":"137","author":"Corradini","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1182\/blood-2009-02-206771","article-title":"BMP\/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression","volume":"114","author":"Kautz","year":"2009","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/ng1274","article-title":"Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis","volume":"36","author":"Papanikolaou","year":"2004","journal-title":"Nat. Genet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng1053","article-title":"Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis","volume":"33","author":"Roetto","year":"2003","journal-title":"Nat. Genet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1182\/blood-2005-05-1845","article-title":"Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin","volume":"106","author":"Lin","year":"2005","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization","volume":"306","author":"Nemeth","year":"2004","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3324\/haematol.10701","article-title":"Juvenile hemochromatosis caused by a novel combination of hemojuvelin G320V\/R176C mutations in a 5-year old girl","volume":"92","author":"Lok","year":"2007","journal-title":"Haematologica"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1089\/gtmb.2010.0056","article-title":"Hemojuvelin and hepcidin genes sequencing in Brazilian patients with primary iron overload","volume":"14","author":"Pereira","year":"2010","journal-title":"Genet. Test Mol. Biomark"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1182\/blood-2004-01-0192","article-title":"Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis","volume":"103","author":"Lanzara","year":"2004","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4669","DOI":"10.1182\/blood-2004-01-0072","article-title":"Genetic abnormalities and juvenile hemochromatosis: Mutations of the HJV gene encoding hemojuvelin","volume":"103","author":"Lee","year":"2004","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1182\/blood-2003-10-3366","article-title":"HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype","volume":"103","author":"Jacolot","year":"2004","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1182\/blood-2005-04-1630","article-title":"A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron","volume":"106","author":"Porto","year":"2005","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.bcmd.2004.08.002","article-title":"Identification of new mutations of hepcidin and hemojuvelin in patients with HFE C282Y allele","volume":"33","author":"Biasiotto","year":"2004","journal-title":"Blood Cells Mol. Dis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00277-009-0705-y","article-title":"Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene","volume":"88","author":"Altes","year":"2009","journal-title":"Ann. Hematol"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1093\/hmg\/ddg225","article-title":"Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis","volume":"12","author":"Cadet","year":"2003","journal-title":"Hum. Mol. Genet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1159\/000243798","article-title":"Rare types of genetic hemochromatosis","volume":"122","author":"Camaschella","year":"2009","journal-title":"Acta Haematol"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/ng1777","article-title":"Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression","volume":"38","author":"Babitt","year":"2006","journal-title":"Nat. Genet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.1182\/blood-2004-12-4844","article-title":"Hepcidin in iron overload disorders","volume":"105","author":"Papanikolaou","year":"2005","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1159\/000208988","article-title":"Hemojuvelin: The hepcidin story continues","volume":"32","author":"Malyszko","year":"2009","journal-title":"Kidney Blood Press. Res"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/ng.335","article-title":"BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism","volume":"41","author":"Andriopoulos","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1172\/JCI31342","article-title":"Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance","volume":"117","author":"Babitt","year":"2007","journal-title":"J. Clin. Invest"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00109-009-0447-2","article-title":"Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV\/BMP\/SMAD","volume":"87","author":"Casanovas","year":"2009","journal-title":"J. Mol. Med. (Berl.)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/ng.320","article-title":"Lack of the bone morphogenetic protein BMP6 induces massive iron overload","volume":"41","author":"Meynard","year":"2009","journal-title":"Nat. Genet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1053\/j.gastro.2011.06.077","article-title":"Iron regulation of hepcidin despite attenuated smad1,5,8 signaling in mice without transferrin receptor 2 or hfe","volume":"141","author":"Corradini","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1172\/JCI25049","article-title":"A mouse model of juvenile hemochromatosis","volume":"115","author":"Huang","year":"2005","journal-title":"J. Clin. Invest"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1172\/JCI25683","article-title":"Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload","volume":"115","author":"Niederkofler","year":"2005","journal-title":"J. Clin. Invest"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cmet.2005.10.010","article-title":"A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression","volume":"2","author":"Wang","year":"2005","journal-title":"Cell Metab"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/75534","article-title":"The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22","volume":"25","author":"Camaschella","year":"2000","journal-title":"Nat. Genet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20826","DOI":"10.1074\/jbc.274.30.20826","article-title":"Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family","volume":"274","author":"Kawabata","year":"1999","journal-title":"J. Biol. Chem"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1182\/blood-2004-08-3042","article-title":"Hepcidin is decreased in TFR2 hemochromatosis","volume":"105","author":"Nemeth","year":"2005","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1136\/gut.2004.062018","article-title":"First phenotypic description of transferrin receptor 2 knockout mouse, and the role of hepcidin","volume":"54","author":"Wallace","year":"2005","journal-title":"Gut"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36862","DOI":"10.1074\/jbc.M706720200","article-title":"HFE modulates transferrin receptor 2 levels in hepatoma cells via interactions that differ from transferrin receptor 1-HFE interactions","volume":"282","author":"Chen","year":"2007","journal-title":"J. Biol. Chem"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cmet.2007.11.016","article-title":"The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression","volume":"7","author":"Schmidt","year":"2008","journal-title":"Cell Metab"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.abb.2008.02.041","article-title":"HFE association with transferrin receptor 2 increases cellular uptake of transferrin-bound iron","volume":"474","author":"Waheed","year":"2008","journal-title":"Arch. Biochem. Biophys"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10653","DOI":"10.1073\/pnas.162360699","article-title":"Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis","volume":"99","author":"Fleming","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"990","DOI":"10.2169\/internalmedicine.44.990","article-title":"A Japanese family with ferroportin disease caused by a novel mutation of SLC40A1 gene: Hyperferritinemia associated with a relatively low transferrin saturation of iron","volume":"44","author":"Koyama","year":"2005","journal-title":"Intern. Med"},{"key":"ref_66","first-page":"e92","article-title":"Homozygous p.M172K mutation of the TFR2 gene in an Italian family with type 3 hereditary hemochromatosis and early onset iron overload","volume":"91","author":"Majore","year":"2006","journal-title":"Haematologica"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1182\/blood-2002-01-0133","article-title":"Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: Identification of a novel TfR2 mutation","volume":"100","author":"Mattman","year":"2002","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.jhep.2010.05.016","article-title":"Ferroportin disease: A systematic meta-analysis of clinical and molecular findings","volume":"53","author":"Mayr","year":"2010","journal-title":"J. Hepatol"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4096","DOI":"10.1182\/blood-2004-11-4502","article-title":"In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations","volume":"105","author":"Schimanski","year":"2005","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"19906","DOI":"10.1074\/jbc.M000713200","article-title":"A novel mammalian iron-regulated protein involved in intracellular iron metabolism","volume":"275","author":"Abboud","year":"2000","journal-title":"J. Biol. Chem"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1146\/annurev.med.57.121304.131310","article-title":"Hemochromatosis: Genetics and pathophysiology","volume":"57","author":"Beutler","year":"2006","journal-title":"Annu. Rev. Med"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1365-2141.2005.05815.x","article-title":"Genetic and clinical heterogeneity of ferroportin disease","volume":"131","author":"Cremonesi","year":"2005","journal-title":"Br. J. Haematol"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1182\/blood-2003-02-0439","article-title":"Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations","volume":"102","author":"Hetet","year":"2003","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1093\/ajcn\/82.5.1102","article-title":"Effect of ferroportin Q248H polymorphism on iron status in African children","volume":"82","author":"Kasvosve","year":"2005","journal-title":"Am. J. Clin. Nutr"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/j.1572-0241.2005.40998.x","article-title":"The evaluation of hyperferritinemia: An updated strategy based on advances in detecting genetic abnormalities","volume":"100","author":"Schved","year":"2005","journal-title":"Am. J. Gastroenterol"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.blre.2008.03.001","article-title":"Current approach to hemochromatosis","volume":"22","author":"Brissot","year":"2008","journal-title":"Blood Rev"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S1079-9796(03)00036-6","article-title":"Phenotypic expression of the C282Y\/Q283P compound heterozygosity in HFE and molecular modeling of the Q283P mutation effect","volume":"30","author":"Dupradeau","year":"2003","journal-title":"Blood Cells Mol. Dis"},{"key":"ref_78","first-page":"107","article-title":"The clinical relevance of new insights in iron transport and metabolism","volume":"3","author":"Brissot","year":"2004","journal-title":"Curr. Hematol. Rep"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"(2010). EASL clinical practice guidelines for HFE hemochromatosis. J. Hepatol., 53, 3\u201322.","DOI":"10.1016\/j.jhep.2010.03.001"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Brissot, P., and de Bels, F (2006). Current approaches to the management of hemochromatosis. Hematol. Am. Soc. Hematol. Educ. Program, 36\u201341.","DOI":"10.1182\/asheducation-2006.1.36"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Van Bokhoven, M.A., van Deursen, C.T., and Swinkels, D.W. (2011). Diagnosis and management of hereditary haemochromatosis. BMJ, 342.","DOI":"10.1136\/bmj.c7251"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.cca.2010.12.007","article-title":"Advantage of high-resolution melting curve analysis over conformation-sensitive gel electrophoresis for mutational screening of BRCA1 and BRCA2 genes","volume":"412","author":"Cardenosa","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1515\/CCLM.2011.654","article-title":"Genotyping of the hemochromatosis HFE p.H63D and p.C282Y mutations by high-resolution melting with the Rotor-Gene 6000((R)) instrument","volume":"49","author":"Santos","year":"2011","journal-title":"Clin. Chem. Lab. Med"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0009-9120(01)00252-1","article-title":"An unusual melting curve profile in LightCycler multiplex genotyping of the hemochromatosis H63D\/C282Y gene mutations","volume":"34","author":"Tag","year":"2001","journal-title":"Clin. Biochem"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1515\/CCLM.2010.281","article-title":"High resolution melting for the identification of mutations in the iron responsive element of the ferritin light chain gene","volume":"48","author":"Castiglioni","year":"2011","journal-title":"Clin. Chem. Lab. Med"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.cca.2010.11.027","article-title":"High resolution melting analysis for the detection of SLC25A13 gene mutations in Taiwan","volume":"412","author":"Lin","year":"2011","journal-title":"Clin. Chim. Acta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/2\/1497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:48:42Z","timestamp":1760219322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/2\/1497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,1]]},"references-count":86,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2012,2]]}},"alternative-id":["ijms13021497"],"URL":"https:\/\/doi.org\/10.3390\/ijms13021497","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,1]]}}}