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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 8
Aug.  2019
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Article Contents

Genetic diagnosis of hereditary hemochromatosis

DOI: 10.3969/j.issn.1001-5256.2019.08.004
  • Received Date: 2019-05-16
  • Published Date: 2019-08-20
  • Iron overload is not rarely seen in clinical practice, and hemochromatosis involving the liver is the most common type of iron overload. There is an extremely low incidence rate of the classic form of HFE hereditary hemochromatosis in the Asian population, which is different from the genetic background of the Caucasian population. European and American studies and international guidelines mainly focus on the HFE type, and there is low consistency between guidelines, with a lack of data from the Asian population. Therefore, with reference to the pathogenic genes of hereditary hemochromatosis and related data in China, this article discusses the genetic diagnosis of hereditary hemochromatosis, in order to provide a reference for the diagnosis and studies of hemochromatosis in the Chinese population.

     

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  • [1] CZAJA AJ. Review article:Iron disturbances in chronic liver diseases other than haemochromatosis-pathogenic, prognostic, and therapeutic implications[J]. Aliment Pharmacol Ther, 2019, 49 (6) :681-701.
    [2] European Association for the Study of the Liver. EASL clinical practice guidelines for HFE hemochromatosis[J]. J Hepatol, 2010, 53 (1) :3-22.
    [3] BACON BR, ADAMS PC, KOWDLEY KV, et al. Diagnosis and management of hemochromatosis:2011 practice guideline by the American Association for the Study of Liver Diseases[J].Hepatology, 2011, 54 (1) :328-343.
    [4] FITZSIMONS EJ, CULLIS JO, THOMAS DW, et al. Diagnosis and therapy of genetic haemochromatosis (review and 2017update) [J]. Br J Haematol, 2018, 181 (3) :293-303.
    [5] VANCLOOSTER A, CASSIMAN D, van STEENBERGEN W, et al. The quality of hereditary haemochromatosis guidelines:A comparative analysis[J]. Clin Res Hepatol Gastroenterol, 2015, 39 (2) :205-214.
    [6] SIMON M, BOUREL M, FAUCHET R, et al. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis[J]. Gut, 1976, 17 (5) :332-334.
    [7] CARTWRIGHT GE, EDWARDS CQ, KRAVITZ K, et al. Hereditary hemochromatosis. Phenotypic expression of the disease[J]. N Engl J Med, 1979, 301 (4) :175-179.
    [8] FEDER JN, GNIRKE A, THOMAS W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis[J]. Nat Genet, 1996, 13 (4) :399-408.
    [9] KANWAR P, KOWDLEY KV. Diagnosis and treatment of hereditary hemochromatosis:An update[J]. Expert Rev Gastroenterol Hepatol, 2013, 7 (6) :517-530.
    [10] ADAMS PC. Epidemiology and diagnostic testing for hemochromatosis and iron overload[J]. Int J Lab Hematol, 2015, 37 (Suppl 1) :25-30.
    [11] DEUGNIER Y, MORCET J, LAINF, et al. Reduced phenotypic expression in genetic hemochromatosis with time:Role of exposure to non-genetic modifiers[J]. J Hepatol, 2019, 70 (1) :118-125.
    [12] WANG Y, DU Y, LIU G, et al. Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis[J]. Int J Hematol, 2017, 105 (4) :521-525.
    [13] LV T, ZHANG W, XU A, et al. Non-HFE mutations in haemochromatosis in China:Combination of heterozygous mutations involving HJV signal peptide variants[J]. J Med Genet, 2018, 55 (10) :650-660.
    [14] ZHANG W, LV T, HUANG J, et al. Type 4B hereditary hemochromatosis associated with a novel mutation in the SLC40A1gene:A case report and a review of the literature[J]. Medicine (Baltimore) , 2017, 96 (38) :e8064.
    [15] TSUI WM, LAM PW, LEE KC, et al. The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic patients:Multicentre retrospective study[J]. Hong Kong Med J, 2000, 6 (2) :153-158.
    [16] YE K, CAO C, LIN X, et al. Natural selection on HFE in Asian populations contributes to enhanced non-heme iron absorption[J]. BMC Genet, 2015, 16:61.
    [17] ROETTO A, TOTARO A, CAZZOLA M, et al. Juvenile hemochromatosis locus maps to chromosome 1q[J]. Am J Hum Genet, 1999, 64 (5) :1388-1393.
    [18] PAPANIKOLAOU G, PAPAIOANNOU M, POLITOU M, et al.Genetic heterogeneity underlies juvenile hemochromatosis phenotype:Analysis of three families of northern Greek origin[J]. Blood Cells Mol Dis, 2002, 29 (2) :168-173.
    [19] PAPANIKOLAOU G, SAMUELS ME, LUDWIG EH, et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis[J]. Nat Genet, 2004, 36 (1) :77-82.
    [20] BABITT JL, HUANG FW, WRIGHTING DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression[J]. Nat Genet, 2006, 38 (5) :531-539.
    [21] ROETTO A, PAPANIKOLAOU G, POLITOU M, et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis[J]. Nat Genet, 2003, 33 (1) :21-22.
    [22] ZUMERLE S, MATHIEU JR, DELGA S, et al. Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype[J]. Blood, 2014, 123 (23) :3646-3650.
    [23] CAMASCHELLA C, ROETTO A, CALA, et al. The gene TFR2is mutated in a new type of haemochromatosis mapping to7q22[J]. Nat Genet, 2000, 25 (1) :14-15.
    [24] PIETRANGELO A, CALEFFI A, HENRION J, et al. Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes[J]. Gastroenterology, 2005, 128 (2) :470-479.
    [25] CORRADINI E, ROZIER M, MEYNARD D, et al. Iron regulation of hepcidin despite attenuated Smad1, 5, 8 signaling in mice without transferrin receptor 2 or Hfe[J]. Gastroenterology, 2011, 141 (5) :1907-1914.
    [26] ZHANG W, XU A, LI Y, et al. A novel SLC40A1 p. Y333H mutation with gain of function of ferroportin:A recurrent cause of haemochromatosis in China[J]. Liver Int, 2019, 39 (6) :1120-1127.
    [27] PIETRANGELO A. Ferroportin disease:Pathogenesis, diagnosis and treatment[J]. Haematologica, 2017, 102 (12) :1972-1984.
    [28] NJAJOU OT, VAESSEN N, JOOSSE M, et al. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis[J]. Nat Genet, 2001, 28 (3) :213-214.
    [29] SHAM RL, PHATAK PD, WEST C, et al. Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin mutation and unique clinical features[J]. Blood Cells Mol Dis, 2005, 34 (2) :157-161.
    [30] ALTAMURA S, KESSLER R, GRNE HJ, et al. Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload[J]. Cell Metab, 2014, 20 (2) :359-367.
    [31] CHEN SR, YANG LQ, CHONG YT, et al. Novel gain of function mutation in the SLC40A1 gene associated with hereditary haemochromatosis type 4[J]. Intern Med J, 2015, 45 (6) :672-676.
    [32] PIETRANGELO A, MONTOSI G, TOTARO A, et al. Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene[J]. N Engl J Med, 1999, 341 (10) :725-732.
    [33] MONTOSI G, DONOVAN A, TOTARO A, et al. Autosomaldominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene[J]. J Clin Invest, 2001, 108 (4) :619-623.
    [34] ZOHN IE, de DOMENICO I, POLLOCK A, et al. The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease[J]. Blood, 2007, 109 (10) :4174-4180.
    [35] LE LAN C, MOSSER A, ROPERT M, et al. Sex and acquired cofactors determine phenotypes of ferroportin disease[J].Gastroenterology, 2011, 140 (4) :1199-1207.
    [36] KONO S. Aceruloplasminemia:An update[J]. Int Rev Neurobiol, 2013, 110:125-151.
    [37] MIYAJIMA H, NISHIMURA Y, MIZOGUCHI K, et al. Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration[J]. Neurology, 1987, 37 (5) :761-767.
    [38] HARRIS ZL, TAKAHASHI Y, MIYAJIMA H, et al. Aceruloplasminemia:Molecular characterization of this disorder of iron metabolism[J]. Proc Natl Acad Sci U S A, 1995, 92 (7) :2539-2543.
    [39] XU W, ZHI Y, YUAN Y, et al. Correlations between abnormal iron metabolism and non-motor symptoms in Parkinson's disease[J]. J Neural Transm (Vienna) , 2018, 125 (7) :1027-1032.
    [40] LI XH, LU Y, LING Y, et al. Clinical and molecular characterization of Wilson's disease in China:Identification of 14 novel mutations[J]. BMC Med Genet, 2011, 12:6.
    [41] HAYASHI A, WADA Y, SUZUKI T, et al. Studies on familial hypotransferrinemia:Unique clinical course and molecular pathology[J]. Am J Hum Genet, 1993, 53 (1) :201-213.
    [42] HEILMEYER L, KELLER W, VIVELL O, et al. Congenital atransferrinemia in a 7-year-old girl[J]. Dtsch Med Wochenschr, 1961, 86:1745-1751.
    [43] ATHIYARATH R, ARORA N, FUSTER F, et al. Two novel missense mutations in iron transport protein transferrin causing hypochromic microcytic anaemia and haemosiderosis:Molecular characterization and structural implications[J]. Br J Haematol, 2013, 163 (3) :404-407.
    [44] CHEN C, WEN S, TAN X. Molecular analysis of a novel case of congenital atransferrinemia[J]. Acta Haematol, 2009, 122 (1) :27-28.
    [45] YACHIE A, NIIDA Y, WADA T, et al. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1deficiency[J]. J Clin Invest, 1999, 103 (1) :129-135.
    [46] RADHAKRISHNAN N, YADAV SP, SACHDEVA A, et al. Human heme oxygenase-1 deficiency presenting with hemolysis, nephritis, and asplenia[J]. J Pediatr Hematol Oncol, 2011, 33 (1) :74-78.
    [47] BHUVA M, SEN S, ELSEY T, et al. Sequence analysis of exon1 of the ferritin light chain (FTL) gene can reveal the rare disorder‘hereditary hyperferritinaemia without cataracts’[J]. Br J Haematol, 2019, 184 (6) :1037-1040.
    [48] FERRO E, CAPRA AP, ZIRILLI G, et al. FTL c.-168G>C mutation in hereditary hyperferritinemia cataract syndrome:A new Italian family[J]. Pediatr Dev Pathol, 2018, 21 (5) :456-460.
    [49] MATTILA RM, SAINIO A, JRVELINEN M, et al. A novel double nucleotide variant in the ferritin-L iron-responsive element in a Finnish patient with hereditary hyperferritinaemia-cataract syndrome[J]. Acta Ophthalmol, 2018, 96 (1) :95-99.
    [50] YIN D, KULHALLI V, WALKER AP. Raised serum ferritin concentration in hereditary hyperferritinemia cataract syndrome is not a marker for iron overload[J]. Hepatology, 2014, 59 (3) :1204-1206.
    [51] KATO J, FUJIKAWA K, KANDA M, et al. A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload[J]. Am J Hum Genet, 2001, 69 (1) :191-197.
    [52] DAHER R, KANNENGIESSER C, HOUAMEL D, et al. Heterozygous mutations in BMP6 pro-peptide lead to inappropriate hepcidin synthesis and moderate iron overload in humans[J].Gastroenterology, 2016, 150 (3) :672-683.
    [53] LE GAC G, GOURLAOUEN I, KA C, et al. The p. Leu96Pro missense mutation in the BMP6 gene is repeatedly associated with hyperferritinemia in patients of French origin[J]. Gastroenterology, 2016, 151 (4) :769-770.
    [54] PIUBELLI C, CASTAGNA A, MARCHI G, et al. Identification of new BMP6 pro-peptide mutations in patients with iron overload[J]. Am J Hematol, 2017, 92 (6) :562-568.
    [55] McDONALD CJ, RISHI G, SECONDES ES, et al. Evaluation of a bone morphogenetic protein 6 variant as a cause of iron loading[J]. Hum Genomics, 2018, 12 (1) :23.
    [56] BARTON JC. Hemochromatosis and iron overload:From bench to clinic[J]. Am J Med Sci, 2013, 346 (5) :403-412.
    [57] OLYNYK JK, CULLEN DJ, AQUILIA S, et al. A populationbased study of the clinical expression of the hemochromatosis gene[J]. N Engl J Med, 1999, 341 (10) :718-724.
    [58] HAYASHI H, WAKUSAWA S, MOTONISHI S, et al. Genetic background of primary iron overload syndromes in Japan[J].Intern Med, 2006, 45 (20) :1107-1111.
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