Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis
Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutati...
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creator | del-Castillo-Rueda, Alejandro Moreno-Carralero, María-Isabel Cuadrado-Grande, Nuria Álvarez-Sala-Walther, Luis-Antonio Enríquez-de-Salamanca, Rafael Méndez, Manuel Morán-Jiménez, María-Josefa |
description | Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis.
We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis.
We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene.
Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype.
► Hereditary hemochromatosis is clinically and genetically heterogeneous. ► Genetic analysis is challenged when mutation C2812Y in HFE is absent. ► We found published and unpublished mutations in HFE, TFR2 and SLC40A1 genes. |
doi_str_mv | 10.1016/j.gene.2012.07.069 |
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We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis.
We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene.
Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype.
► Hereditary hemochromatosis is clinically and genetically heterogeneous. ► Genetic analysis is challenged when mutation C2812Y in HFE is absent. ► We found published and unpublished mutations in HFE, TFR2 and SLC40A1 genes.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2012.07.069</identifier><identifier>PMID: 22890139</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Cation Transport Proteins - genetics ; DNA - genetics ; Dysmetabolic iron overload syndrome (DIOS) ; early diagnosis ; Female ; Ferroportin (SLC40A1) ; genes ; genetic techniques and protocols ; Genotype ; hemochromatosis ; Hemochromatosis - complications ; Hemochromatosis - diagnosis ; Hemochromatosis - genetics ; Hemochromatosis Protein ; Hereditary hemochromatosis ; heterozygosity ; Heterozygote ; HFE ; Histocompatibility Antigens Class I - genetics ; homozygosity ; Homozygote ; Humans ; Hyperferritinemia ; Iron Overload - diagnosis ; Iron Overload - etiology ; Male ; Membrane Proteins - genetics ; metabolic syndrome ; Middle Aged ; mutation ; Mutation - genetics ; patients ; Phenotype ; Polymerase Chain Reaction ; Receptors, Transferrin - genetics ; risk ; Transferrin receptor 2 (TFR2)</subject><ispartof>Gene, 2012-10, Vol.508 (1), p.15-20</ispartof><rights>2012</rights><rights>Copyright © 2012. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-df695e152bd52c865605bb73fa0371a914561be7b3e5d446981e0ec4b1288cc73</citedby><cites>FETCH-LOGICAL-c380t-df695e152bd52c865605bb73fa0371a914561be7b3e5d446981e0ec4b1288cc73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.gene.2012.07.069$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22890139$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>del-Castillo-Rueda, Alejandro</creatorcontrib><creatorcontrib>Moreno-Carralero, María-Isabel</creatorcontrib><creatorcontrib>Cuadrado-Grande, Nuria</creatorcontrib><creatorcontrib>Álvarez-Sala-Walther, Luis-Antonio</creatorcontrib><creatorcontrib>Enríquez-de-Salamanca, Rafael</creatorcontrib><creatorcontrib>Méndez, Manuel</creatorcontrib><creatorcontrib>Morán-Jiménez, María-Josefa</creatorcontrib><title>Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis</title><title>Gene</title><addtitle>Gene</addtitle><description>Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis.
We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis.
We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene.
Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype.
► Hereditary hemochromatosis is clinically and genetically heterogeneous. ► Genetic analysis is challenged when mutation C2812Y in HFE is absent. ► We found published and unpublished mutations in HFE, TFR2 and SLC40A1 genes.</description><subject>Adult</subject><subject>Cation Transport Proteins - genetics</subject><subject>DNA - genetics</subject><subject>Dysmetabolic iron overload syndrome (DIOS)</subject><subject>early diagnosis</subject><subject>Female</subject><subject>Ferroportin (SLC40A1)</subject><subject>genes</subject><subject>genetic techniques and protocols</subject><subject>Genotype</subject><subject>hemochromatosis</subject><subject>Hemochromatosis - complications</subject><subject>Hemochromatosis - diagnosis</subject><subject>Hemochromatosis - genetics</subject><subject>Hemochromatosis Protein</subject><subject>Hereditary hemochromatosis</subject><subject>heterozygosity</subject><subject>Heterozygote</subject><subject>HFE</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>homozygosity</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Hyperferritinemia</subject><subject>Iron Overload - diagnosis</subject><subject>Iron Overload - etiology</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>metabolic syndrome</subject><subject>Middle Aged</subject><subject>mutation</subject><subject>Mutation - genetics</subject><subject>patients</subject><subject>Phenotype</subject><subject>Polymerase Chain Reaction</subject><subject>Receptors, Transferrin - genetics</subject><subject>risk</subject><subject>Transferrin receptor 2 (TFR2)</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1P3DAQhq0KVBbaP9AD9ZEDSf0RJ7bEZbViS6WFSgXOluNMWK828db2UvXf43ShR-Yyl2femXkQ-kJJSQmtv23KJxihZISykjQlqdUHNKOyUQUhXB6hGeGNLCil6gSdxrghuYRgH9EJY1IRytUM3d3uk0nOjxG7Eac14Jvl9SV-WP5il9iMHb5fLSoyp3ha9Y_ZZRzGFPEfl9Z4DYO36-AHk3x08RM67s02wufXfoYel9cPi5ti9fP7j8V8VVguSSq6vlYCqGBtJ5iVtaiJaNuG9yafTI2ilahpC03LQXRVVStJgYCtWsqktLbhZ-jikLsL_vceYtKDixa2WzOC30dNp9el4KrOKDugNvgYA_R6F9xgwt8M6cmj3ujpOT151KTR2WMeOn_N37cDdP9H3sRl4OsB6I3X5im4qB_vc4LIjiveiCoTVwcCsodnB0FHm8VZ6FwAm3Tn3XsXvADjwYok</recordid><startdate>20121015</startdate><enddate>20121015</enddate><creator>del-Castillo-Rueda, Alejandro</creator><creator>Moreno-Carralero, María-Isabel</creator><creator>Cuadrado-Grande, Nuria</creator><creator>Álvarez-Sala-Walther, Luis-Antonio</creator><creator>Enríquez-de-Salamanca, Rafael</creator><creator>Méndez, Manuel</creator><creator>Morán-Jiménez, María-Josefa</creator><general>Elsevier B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20121015</creationdate><title>Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis</title><author>del-Castillo-Rueda, Alejandro ; Moreno-Carralero, María-Isabel ; Cuadrado-Grande, Nuria ; Álvarez-Sala-Walther, Luis-Antonio ; Enríquez-de-Salamanca, Rafael ; Méndez, Manuel ; Morán-Jiménez, María-Josefa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-df695e152bd52c865605bb73fa0371a914561be7b3e5d446981e0ec4b1288cc73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Cation Transport Proteins - genetics</topic><topic>DNA - genetics</topic><topic>Dysmetabolic iron overload syndrome (DIOS)</topic><topic>early diagnosis</topic><topic>Female</topic><topic>Ferroportin (SLC40A1)</topic><topic>genes</topic><topic>genetic techniques and protocols</topic><topic>Genotype</topic><topic>hemochromatosis</topic><topic>Hemochromatosis - complications</topic><topic>Hemochromatosis - diagnosis</topic><topic>Hemochromatosis - genetics</topic><topic>Hemochromatosis Protein</topic><topic>Hereditary hemochromatosis</topic><topic>heterozygosity</topic><topic>Heterozygote</topic><topic>HFE</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>homozygosity</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Hyperferritinemia</topic><topic>Iron Overload - diagnosis</topic><topic>Iron Overload - etiology</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>metabolic syndrome</topic><topic>Middle Aged</topic><topic>mutation</topic><topic>Mutation - genetics</topic><topic>patients</topic><topic>Phenotype</topic><topic>Polymerase Chain Reaction</topic><topic>Receptors, Transferrin - genetics</topic><topic>risk</topic><topic>Transferrin receptor 2 (TFR2)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>del-Castillo-Rueda, Alejandro</creatorcontrib><creatorcontrib>Moreno-Carralero, María-Isabel</creatorcontrib><creatorcontrib>Cuadrado-Grande, Nuria</creatorcontrib><creatorcontrib>Álvarez-Sala-Walther, Luis-Antonio</creatorcontrib><creatorcontrib>Enríquez-de-Salamanca, Rafael</creatorcontrib><creatorcontrib>Méndez, Manuel</creatorcontrib><creatorcontrib>Morán-Jiménez, María-Josefa</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>del-Castillo-Rueda, Alejandro</au><au>Moreno-Carralero, María-Isabel</au><au>Cuadrado-Grande, Nuria</au><au>Álvarez-Sala-Walther, Luis-Antonio</au><au>Enríquez-de-Salamanca, Rafael</au><au>Méndez, Manuel</au><au>Morán-Jiménez, María-Josefa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2012-10-15</date><risdate>2012</risdate><volume>508</volume><issue>1</issue><spage>15</spage><epage>20</epage><pages>15-20</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis.
We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis.
We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene.
Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype.
► Hereditary hemochromatosis is clinically and genetically heterogeneous. ► Genetic analysis is challenged when mutation C2812Y in HFE is absent. ► We found published and unpublished mutations in HFE, TFR2 and SLC40A1 genes.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>22890139</pmid><doi>10.1016/j.gene.2012.07.069</doi><tpages>6</tpages></addata></record> |
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subjects | Adult Cation Transport Proteins - genetics DNA - genetics Dysmetabolic iron overload syndrome (DIOS) early diagnosis Female Ferroportin (SLC40A1) genes genetic techniques and protocols Genotype hemochromatosis Hemochromatosis - complications Hemochromatosis - diagnosis Hemochromatosis - genetics Hemochromatosis Protein Hereditary hemochromatosis heterozygosity Heterozygote HFE Histocompatibility Antigens Class I - genetics homozygosity Homozygote Humans Hyperferritinemia Iron Overload - diagnosis Iron Overload - etiology Male Membrane Proteins - genetics metabolic syndrome Middle Aged mutation Mutation - genetics patients Phenotype Polymerase Chain Reaction Receptors, Transferrin - genetics risk Transferrin receptor 2 (TFR2) |
title | Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis |
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