{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T11:16:49Z","timestamp":1768735009179,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The adult human body contains about 4 g of iron. About 1\u20132 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g\/dL and ferritin levels below 30 ng\/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.<\/jats:p>","DOI":"10.3390\/genes12121869","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T05:23:02Z","timestamp":1638163382000},"page":"1869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Iron Deficiency Caused by Intestinal Iron Loss\u2014Novel Candidate Genes for Severe Anemia"],"prefix":"10.3390","volume":"12","author":[{"given":"Carolina","family":"Huettmann","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Stelljes","sequence":"additional","affiliation":[{"name":"Medical Clinic D: Hematology, Haemostaseology, Oncology and Pneumology, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sugirthan","family":"Sivalingam","sequence":"additional","affiliation":[{"name":"Core Unit Bioinformatics Data Analysis, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"},{"name":"Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"},{"name":"Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Fobker","sequence":"additional","affiliation":[{"name":"Center for Laboratory Medicine, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Vrachimis","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Exler","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Wenning","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carola","family":"Wempe","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Penke","sequence":"additional","affiliation":[{"name":"Oncological Clinic, St. Franziskus Hospital, Franziskusstra\u00dfe 6, 49393 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-8632","authenticated-orcid":false,"given":"Andreas","family":"Buness","sequence":"additional","affiliation":[{"name":"Core Unit Bioinformatics Data Analysis, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"},{"name":"Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"},{"name":"Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-2519","authenticated-orcid":false,"given":"Kerstin U.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Bonn, Medical Faculty University of Bonn, 53113 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3778-510X","authenticated-orcid":false,"given":"Martina U.","family":"Muckenthaler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, 69117 Heidelberg, Germany"},{"name":"Molecular Medicine Partnership Unit (MMPU), 69117 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5237-961X","authenticated-orcid":false,"given":"Andrea U.","family":"Steinbicker","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany"},{"name":"Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1182\/blood-2013-06-508325","article-title":"A systematic analysis of global anemia burden from 1990 to 2010","volume":"123","author":"Kassebaum","year":"2014","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.3390\/nu5083034","article-title":"Out of balance\u2014Systemic iron homeostasis in iron-related disorders","volume":"5","author":"Steinbicker","year":"2013","journal-title":"Nutrients"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/978-90-481-9485-8_22","article-title":"Epidemiology of rare anaemias in Europe","volume":"686","author":"Gulbis","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","unstructured":"(2021, November 23). European Network for Rare and Congenital Anaemias, Available online: https:\/\/rarediseases.info.nih.gov\/organizations\/872."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1182\/blood-2012-02-411470","article-title":"Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1\/5\/8 signaling","volume":"120","author":"Latour","year":"2012","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fleming, M.D. (2008). The regulation of hepcidin and its effects on systemic and cellular iron metabolism. Am. Soc. Hematol. Educ. Program, 151\u2013158.","DOI":"10.1182\/asheducation-2008.1.151"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Shanmugam, N.K.N., Ellenbogen, S., Trebicka, E., Wang, L., Mukhopadhyay, S., Lacy-Hulbert, A., Gallini, C.A., Garrett, W.S., and Cherayil, B.J. (2012). Tumor necrosis factor \u03b1 inhibits expression of the iron regulating hormone hepcidin in murine models of innate colitis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038136"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1126\/science.1176639","article-title":"ER stress controls iron metabolism through induction of hepcidin","volume":"325","author":"Vecchi","year":"2009","journal-title":"Science"},{"key":"ref_9","first-page":"1349","article-title":"Isotopenmethoden in der An\u00e4miediagnostik","volume":"26","author":"Pixberg","year":"1975","journal-title":"Med. Welt"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1172\/JCI104310","article-title":"The quantitative determination of iron kinetics and hemoglobin synthesis in human subjects","volume":"40","author":"Pollycove","year":"1961","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/00003072-197804000-00014","article-title":"Ferrokinetics: Methods and interpretation","volume":"3","author":"Ricketts","year":"1978","journal-title":"Clin. Nucl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1055\/s-2001-11838","article-title":"Qualit\u00e4tskontrolle der H\u00e4molyserate von Erythrozytenkonzentraten: Ringversuch zur Bestimmung von freiem H\u00e4moglobin [Quality control of hemolysis rate of erythrocyte concentrates: A proficiency test for determination of free hemoglobin]","volume":"36","author":"Tapernon","year":"2000","journal-title":"Anasthesiol. Intensivmed. Notfallmed. Schmerzther"},{"key":"ref_13","unstructured":"(2021, November 23). Genome Aggregation Database. Available online: https:\/\/gnomad.broadinstitute.org."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhu, H., Xia, W., Mo, X.-B., Lin, X., Qiu, Y.-H., Yi, N.-J., Zhang, Y.-H., Deng, F.-Y., and Lei, S.-F. (2016). Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167212"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12935-015-0242-9","article-title":"Analysis of the expression of PHTF1 and related genes in acute lymphoblastic leukemia","volume":"15","author":"Huang","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Andjelkovic, M., Minic, P., Vreca, M., Stojiljkovic, M., Skakic, A., Sovtic, A., Rodic, M., Skodric-Trifunovic, V., Maric, N., and Visekruna, J. (2018). Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205422"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gonzalez-Quereda, L., Rodriguez, M.J., Diaz-Manera, J., Alonso-Perez, J., Gallardo, E., Nascimento, A., Ortez, C., Natera-de Benito, D., Olive, M., and Gonzalez-Mera, L. (2020). Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain. Genes, 11.","DOI":"10.3390\/genes11050539"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.joca.2014.01.010","article-title":"Bone sialoprotein as a potential key factor implicated in the pathophysiology of osteoarthritis","volume":"22","author":"Pesesse","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00775-018-1538-8","article-title":"The unique fold and lability of the 2Fe-2S clusters of NEET proteins mediate their key functions in health and disease","volume":"23","author":"Karmi","year":"2018","journal-title":"J. Biol. Inorg. Chem. JBIC A Publ. Soc. Biol. Inorg. Chem."},{"key":"ref_20","unstructured":"Tamir, S., Paddock, M.L., Darash-Yahana-Baram, M., Holt, S.H., Sohn, Y.S., Agranat, L., Michaeli, D., Stofleth, J.T., Lipper, C.H., and Morcos, F. (2021, November 23). Structure\u2013Function Analysis of NEET Proteins Uncovers Their Role as Key Regulators of Iron and ROS Homeostasis in Health and Disease: SI: Fe\/S Proteins. Available online: http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0167488914003735."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.gene.2015.02.050","article-title":"Identification and characterization of methylation-dependent\/independent DNA regulatory elements in the human SLC9B1 gene","volume":"561","author":"Kumar","year":"2015","journal-title":"Gene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1210\/jc.2003-031286","article-title":"Common variants in glutamine: Fructose-6-phosphate amidotransferase 2 (GFPT2) gene are associated with type 2 diabetes, diabetic nephropathy, and increased GFPT2 mRNA levels","volume":"89","author":"Zhang","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6608","DOI":"10.1093\/nar\/gky461","article-title":"PHD finger protein 1 (PHF1) is a novel reader for histone H4R3 symmetric dimethylation and coordinates with PRMT5-WDR77\/CRL4B complex to promote tumorigenesis","volume":"46","author":"Liu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1083\/jcb.200811072","article-title":"A conserved CCCH-type zinc finger protein regulates mRNA nuclear adenylation and export","volume":"185","author":"Hurt","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13059-014-0569-x","article-title":"An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss","volume":"16","author":"Benton","year":"2015","journal-title":"Genome Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/cr.2015.81","article-title":"Mutation of kri1l causes definitive hematopoiesis failure via PERK-dependent excessive autophagy induction","volume":"25","author":"Jia","year":"2015","journal-title":"Cell Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1152\/physiolgenomics.00130.2014","article-title":"Identification of stable reference genes in differentiating human pluripotent stem cells","volume":"47","author":"Holmgren","year":"2015","journal-title":"Physiol. Genom."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1158\/1078-0432.1119.11.3","article-title":"Allelic losses at 1p36 and 19q13 in gliomas: Correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene","volume":"11","author":"Barbashina","year":"2005","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1158\/0008-5472.CAN-14-2443","article-title":"CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer","volume":"75","author":"Yoshida","year":"2015","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Frezzato, F., Gattazzo, C., Martini, V., Trimarco, V., Teramo, A., Carraro, S., Cabrelle, A., Ave, E., Facco, M., and Zambello, R. (2012). HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039902"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4824","DOI":"10.1038\/s41598-018-22096-0","article-title":"Clinical and genetic characteristics of 251 consecutive patients with macular and cone\/cone-rod dystrophy","volume":"8","author":"Birtel","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.bbamcr.2012.01.014","article-title":"Hepcidin and iron homeostasis","volume":"1823","author":"Ganz","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8780","DOI":"10.1073\/pnas.151179498","article-title":"Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice","volume":"98","author":"Nicolas","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1053\/j.seminhematol.2009.06.005","article-title":"Mutations in the gene encoding DMT1: Clinical presentation and treatment","volume":"46","author":"Iolascon","year":"2009","journal-title":"Semin. Hematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.bcmd.2011.07.004","article-title":"A novel N491S mutation in the human SLC11A2 gene impairs protein trafficking and in association with the G212V mutation leads to microcytic anemia and liver iron overload","volume":"47","author":"Island","year":"2011","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7410","DOI":"10.1073\/pnas.0801318105","article-title":"Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle","volume":"105","author":"Sendamarai","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.exphem.2006.02.004","article-title":"The anemia of \u201chaemoglobin-deficit\u201d (hbd\/hbd) mice is caused by a defect in transferrin cycling","volume":"34","author":"Zhang","year":"2006","journal-title":"Exp. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5494","DOI":"10.1182\/blood-2010-11-319483","article-title":"Targeted deletion of the mouse Mitoferrin1 gene: From anemia to protoporphyria","volume":"117","author":"Troadec","year":"2011","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1172\/JCI40372","article-title":"Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts","volume":"120","author":"Ye","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/pbc.22244","article-title":"Systematic molecular genetic analysis of congenital sideroblastic anemia: Evidence for genetic heterogeneity and identification of novel mutations","volume":"54","author":"Bergmann","year":"2010","journal-title":"Pediatric Blood Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1093\/hmg\/8.5.743","article-title":"Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA\/A)","volume":"8","author":"Allikmets","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/geno.1997.4658","article-title":"Isolation and chromosomal mapping of a novel ATP-binding cassette transporter conserved in mouse and human","volume":"41","author":"Savary","year":"1997","journal-title":"Genomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1182\/blood-2007-02-072520","article-title":"The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload","volume":"110","author":"Camaschella","year":"2007","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/MOP.0b013e3283425591","article-title":"Inherited disorders of iron metabolism","volume":"23","author":"Camaschella","year":"2011","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1182\/blood-2011-04-348698","article-title":"Regulation of TMPRSS6 by BMP6 and iron in human cells and mice","volume":"118","author":"Meynard","year":"2011","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.cmet.2008.09.012","article-title":"The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin","volume":"8","author":"Silvestri","year":"2008","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Winn, N.C., Volk, K.M., and Hasty, A.H. (2020). Regulation of tissue iron homeostasis: The macrophage \u201cferrostat\u201d. JCI Insight, 5.","DOI":"10.1172\/jci.insight.132964"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/jn\/130.1.45","article-title":"Less than 80% of absorbed iron is promptly incorporated into erythrocytes of infants","volume":"130","author":"Fomon","year":"2000","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/0002-9343(68)90069-7","article-title":"Body iron excretion in man: A collaborative study","volume":"45","author":"Green","year":"1968","journal-title":"Am. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF03032686","article-title":"Endogenous iron excretion. A quantitative means to control iron metabolism?","volume":"29","author":"Kreuzer","year":"1991","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1113\/jphysiol.1938.sp003669","article-title":"The absorption and excretion of iron following oral and intravenous administration","volume":"94","author":"McCance","year":"1938","journal-title":"J. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1182\/blood.V5.11.983.983","article-title":"Iron metabolism: The pathophysiology of iron storage","volume":"5","author":"Finch","year":"1950","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s12185-008-0120-5","article-title":"Body iron metabolism and pathophysiology of iron overload","volume":"88","author":"Kohgo","year":"2008","journal-title":"Int. J. Hematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1172\/JCI104982","article-title":"The role of the intestine in iron kinetics","volume":"43","author":"Conrad","year":"1964","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S1097-2765(00)80425-6","article-title":"A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation","volume":"5","author":"McKie","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14725","DOI":"10.1021\/bi051559k","article-title":"Recombinant expression and functional characterization of human hephaestin: A multicopper oxidase with ferroxidase activity","volume":"44","author":"Griffiths","year":"2005","journal-title":"Biochemistry"},{"key":"ref_57","first-page":"306","article-title":"Contribution \u00e0 l\u2019\u00e9tude du m\u00e9tabolisme du fer \u00e0 l\u2019aide du radiofer 59\/26 Fe. I. Quelques donn\u00e9es nouvelles sur l\u2019\u00e9limination r\u00e9nale du fer","volume":"61","author":"Closuit","year":"1953","journal-title":"Arch. Int. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"F606","DOI":"10.1152\/ajprenal.00425.2018","article-title":"Iron handling by the human kidney: Glomerular filtration and tubular reabsorption both contribute to urinary iron excretion","volume":"316","author":"Rennings","year":"2019","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1093\/hmg\/ddx060","article-title":"A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions","volume":"26","author":"Rouzier","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Tamir, S., Zuris, J.A., Agranat, L., Lipper, C.H., Conlan, A.R., Michaeli, D., Harir, Y., Paddock, M.L., Mittler, R., and Cabantchik, Z.I. (2013). Nutrient-deprivation autophagy factor-1 (NAF-1): Biochemical properties of a novel cellular target for anti-diabetic drugs. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061202"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1101\/gad.1779509","article-title":"Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice","volume":"23","author":"Chen","year":"2009","journal-title":"Genes Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nm.3814","article-title":"Anemia: Progress in molecular mechanisms and therapies","volume":"21","author":"Sankaran","year":"2015","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/gim.2016.197","article-title":"Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes","volume":"19","author":"Muramatsu","year":"2017","journal-title":"Genet. 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