Diagnóstico genético en        enfermedades raras del    metabolismo del hierro: Anemias       raras y Hemocromatosis26/2/...
Mayka Sanchez     CLINICAL GENETIC DIAGNOSTICS:Advanced Genetic Diagnostic Unit for Rare      Iron Metabolism Disorders   ...
Iron is essential for life
Iron: a vital biocatalyst that can be toxic                              Fenton reactionHeme proteins(e.g. hemoglobin,cyto...
Systemic Iron homeostasisHeme Hemoglobin                    Hepcidin                          Ferroportin
The importance of Iron balance      Too much…                       …too little                           IRON            ...
Unidad de Diagnóstico Genético Avanzado de Enfermedades           del Metabolismo del Hierrro (UDGAEMH)                   ...
Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders                                                       ...
Procedimiento de petición de análisis Consentimiento informado o CONVENIO firmado es OBLIGATORIO para hacer el estudio. Mu...
Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders  - Puesta   a     punto   de      medida    de    la  ...
Patient’s recruitment (2010-2013)- 13 Hyperferritinemias with cataracts => Seq. IRE FTL: 7 known Mutations, 2 new.     -Po...
Diagnóstico genético en nuevos             casos de IRIDA(iron-refractory iron deficiency Anemia)
Gene TMPRSS6, Protein MATRIPTASE-2•Mask mouse. ENU mutagenesis mice. Inappropriate high hepcidinlevels. Positional cloning...
IRIDA (OMIM #206200)  • Anemia microcítica e hipocroma sin respuesta a hierro oral y  respuesta parcial al hierro intraven...
IRIDA Kindreds. Clinical and Biochemical data We report 4 IRIDA families (6 patients) with 4 NEW mutations in TMPRSS6     ...
IRIDA Kindred A . New Nonsense mutation                 Lys              StopNM_153609.2:c.[2252_2253insT];[2252_2253insT]...
IRIDA Kindred B and C . New Missense mutation                        NM_153609.2:c.[861C>A];[861C>A]                      ...
IRIDA Kindred D. New Missense + frameshift mutationNM_153609.2:c.[76_81delGGTGA];[=]                         NM_153609.2:c...
New mutations in IRIDA patients                                    Mutation 1       Mutation 2                            ...
Conclusiones • Es altamente sugestivo que las variaciones encontradas en estas familias sean causantes de su clínica • Nue...
Hereditary Hemochromatosis type III      Functional characterization ofTransferrin Receptor 2 Gly792Arg mutation
Hereditary Hemochromatosis•Iron-overload genetic disease. Increased dietary iron absorption.•Hepatic iron accumulation. He...
Type III Hereditary Hemochromatosis – TFR2 • Type III HH was first described in two Sicilian families by Clara Camaschella...
Case 23 and Case 7. Atypical HemochromatosisProband Case 23:                               Proband Case 7:- Woman. 57 year...
TFR2 Hemochromatosis. Gly792Arg mutation                   CASE 23                          CASE 7                        ...
TFR2 Gly792Arg mutationVARIANT FOUND IN TRF2 GENErs 80338891: NM_003277: c.[2374 G>A]+[2374 G>A];NP_003218.2: p.Gly792Arg;...
Functional implication of TFR2 G792R mutation                          N-FLAG           Cloning and                       ...
Permeablized Cells  C-Flag WILDTYPE TFR2                 C-FLAG TFR2mut-G792R                         Anti-flag ONLY      ...
Permeablized Cells  N-Flag WILDTYPE TFR2                 N-FLAG TFR2mut-G792R                         Anti-flag ONLY      ...
NON-Permeablized Cells  C-Flag WILDTYPE TFR2                 C-FLAG TFR2mut-G792R                         Anti-flag ONLY  ...
Bioinformatic studies of TFR2 G792R mutationrs 80338891: NM_003277: c.[2374 G>A];[2374 G>A]; NP_003218.2: p.Gly792Arg     ...
Conclusions• Genetic analysis of TFR2 revealed a previously described butuncharacterized change Gly792Arg in 2 Spanish fam...
Proyecto hiperferritinemia
Agradecimientos•Iron and cancer group. Mayka Sanchez’s lab (IMPPC)      • Dr. Ricky Joshi      •Francisco Fuster•Advanced ...
Gracias por vuestra atención!                         Jefe:                                               Servicios       ...
Gracias por vuestra atención!                              Mayka Sanchez                     CLINICAL GENETIC DIAGNOSTICS:...
Propuesta- Estancias en la UDGAEMHEstamos interesados en formar a médicos especializados (especialmentehematólogos) en téc...
Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders                                                       ...
Gracias por vuestra atención!Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders                          ...
Diagnóstico genético en enfermedades raras del metabolismo del hierro: Anemias raras y Hemocromatosis
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Diagnóstico genético en enfermedades raras del metabolismo del hierro: Anemias raras y Hemocromatosis

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Seminario dirigido por la Dra. Mayka Sánchez, Principal Investigator. Iron and Cancer Group Head of the Advanced Genetic Diagnostic Unit of Rare Iron Disorders Institute of Predictive and Personalized Medicine of Cancer (IMPPC). Consulta el vídeo de la presentación después de la última diapositiva.

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  • GIFEn la actualidad somos 93 miembros en el GIF de 55 centros hospitalarios, centros de asistencia primaria o centros de investigación . Thesestudieshavebeen done in a newlycreatedDiagnotic service named : Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders to diagnose Rare Iron Metabolism DisordersWe have established the genetic diagnosis for 19 genes responsible for 5 groups of iron-related diseases (hemochromatois, hyperferritinemia, sideroblastic anemia, non-sideroblasticanaemia and CDA) This service is advertised in the European and American portals: ORPHANET AND GENETESTCounts with the support of national and intyernational medical networks, such as the GIF
  • These studies have been done in a newly created Diagnotic service named : Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders to diagnose Rare Iron Metabolism DisordersWe have established the genetic diagnosis for 19 genes responsible for 5 groups of iron-related diseases (hemochromatois, hyperferritinemia, sideroblastic anemia, non-sideroblastic anaemia and CDA) This service is advertised in the European and American portals: ORPHANET AND GENETESTCounts with the support of national and intyernational medical networks, such as the GIF
  • Thesestudieshavebeen done in a newlycreatedDiagnotic service named : Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders to diagnose Rare Iron Metabolism DisordersWe have established the genetic diagnosis for 19 genes responsible for 5 groups of iron-related diseases (hemochromatois, hyperferritinemia, sideroblastic anemia, non-sideroblasticanaemia and CDA) This service is advertised in the European and American portals: ORPHANET AND GENETESTCounts with the support of national and intyernational medical networks, such as the GIF
  • These studies have been done in a newly created Diagnotic service named : Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders to diagnose Rare Iron Metabolism DisordersWe have established the genetic diagnosis for 19 genes responsible for 5 groups of iron-related diseases (hemochromatois, hyperferritinemia, sideroblastic anemia, non-sideroblastic anaemia and CDA) This service is advertised in the European and American portals: ORPHANET AND GENETESTCounts with the support of national and intyernational medical networks, such as the GIF
  • Diagnóstico genético en enfermedades raras del metabolismo del hierro: Anemias raras y Hemocromatosis

    1. 1. Diagnóstico genético en enfermedades raras del metabolismo del hierro: Anemias raras y Hemocromatosis26/2/2013 Hospital Vall de Hebrón
    2. 2. Mayka Sanchez CLINICAL GENETIC DIAGNOSTICS:Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders RESEARCH: Iron & Cancer Postdocs Ricky Joshi, PhD Maya Shvarstman, PhD Technicians Erica Morán, PhD Jessica Aranda PhD student Sara Luscieti Bioinformatician Francisco Fuster
    3. 3. Iron is essential for life
    4. 4. Iron: a vital biocatalyst that can be toxic Fenton reactionHeme proteins(e.g. hemoglobin,cytochromes) e- H 2O 2 Anti-oxidant defenses Fe-S cluster (e.g. proteins of Fe2+ Fe3+ . mitochondrial e- transport) OH Oxidative damageDi-iron proteins(e.g. ribonucleotidereductase) e-
    5. 5. Systemic Iron homeostasisHeme Hemoglobin Hepcidin Ferroportin
    6. 6. The importance of Iron balance Too much… …too little IRON DISEASE Overload Deficiency Hereditary Hemochromatosis Anemia Hepatic Cancer
    7. 7. Unidad de Diagnóstico Genético Avanzado de Enfermedades del Metabolismo del Hierrro (UDGAEMH) Jefe: Servicios • Dra. Mayka Sánchez - Hepcidina sérica/plasmática (ELISA) Técnicos: • Dr. Erica Morán - Diagnóstico Genético de • Jessica Aranda GIF enfermedades raras del metabolismo Medical Doctors del hierro networkhttp://www.imppc.org/resources-and-services/index.htmludgaemh@imppc.orgAcreditación de Calidad:EMQN EQA en HH-HFEDesignada como unidad EXPERTA por ORPHANETAcreditación asistencial Generalitat Catalunya
    8. 8. Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders PRICE CATEGORIES GENE DISEASE OMIM (euros) HFE HH1 120 235200 IRON Classical Hemochromatosis HAMP HH2 (juvenile form) 100 613313 OVERLOAD Non-HFE Hemochromatosis HFE2 HH2 (juvenile form) 100 602390 TFR2 HH3 200 604250 SLC40A1 HH4 160 606069 FTL Hereditary hyperferretinemia with cataracts 50 600886HYPERFERRITI Hyperferritinemia FTL Benign Hyperferretinemia 100 600886 NEMIA FTH Hyperferretinemia with iron overload 100 134770 ALAS2 XLSA 150 300751 STEAP3 Sideroblastic anemia associated to STEAP3 150 609671 ABCB7 XLSA with ataxia 100 301310 Sideroblastic GLRX5 SA with hepatic iron overload 100 205950 SLC25A38 Non syndromic autosomal recessive CSA 100 205950 RARE IRON- CP Aceruloplasminemia 230 604290 RELATED TF Hypotransferrinemia 250 209300 ANEMIAS Non-sideroblastic Familiar microcytic hypochromic anemia with SLC11A2 hepatic iron overload 200 206100 TMPRSS6 IRIDA, Iron-refractory iron deficient anemia 200 206200 CDAN1 CDA type I 250 224120 Congenital dyserythropoietic SEC23B CDA type II 250 224100 anemia KLF1 Unclassified CDA 150 NA Precios exentos de IVA si viene de un HOSPITAL
    9. 9. Procedimiento de petición de análisis Consentimiento informado o CONVENIO firmado es OBLIGATORIO para hacer el estudio. Muestra: 3 tubos de EDTA (15 ml sangre) + 1 tubo suero sin anticoagulantes Envío de lunes a miércoles de 9.00 a 17.00h Contactar por email: udgaemh@imppc.org http://www.imppc.org/resources-and-services/genetic-diagnostics-metabolism-disorders/es_procedudgaemh.html http://www.imppc.org/resources-and-services/index.html
    10. 10. Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders - Puesta a punto de medida de la HEPCIDINA SERICA/PLASMATICA por ELISA -La hepcidina es la hormona que controla el metabolismo del Hepcidin hierro, mediante el bloqueo de la absorción de hierro por el intestino y el bloqueo de la liebración de hierro de los macrófagos. La hepcidina ejerce su función sobre la ferroportina Ferroportin -Niveles muy bajos de hepcidina se dan en HEMOCROMATOSIS HEREDITARIAS Inhibition of : -Niveles altos/normales de hepcidina se dan en IRIDA, lo que Duodenal iron la diferencia de otras anemias como una anemia ferropenica absorption and nutricional, anemia debida a enfermedad celíaca, una anemia macrophage iron debida a talasemias, deficiencia de DMT1, atransferrinemia release (estas otras anemias presentan niveles bajos de hepcidina).
    11. 11. Patient’s recruitment (2010-2013)- 13 Hyperferritinemias with cataracts => Seq. IRE FTL: 7 known Mutations, 2 new. -Poster número PO-382. Erica Morán et al. Congreso de Nacional Hematología 2010. -Chapter of book 2010. The IRP/IRE regulatory network. ISBN 979-953-307-162-5, InTech -2 NEW MUTATIONS Publication in OJRD Luscieti et al., 2013. IF: 5.074 (2011 JCR).- 2 hyperferretinemias without cataracts => Seq. FTL / FTH, No mutations.- 26 Hemochromatosis => Seq. genes HFE, TFR2, HAMP, HJV, SLC40A1. -1 case C282Y HFE. -4 cases TFR2, molecular studies ongoing, 3 NEW MUTATIONS. Publication in preparation -3 cases SLC40A1 (FPN), 2 NEW MUTATIONS- 10 Sideroblástic Anemias (CSA) => Seq. genes ALAS2, SLC25A38, ABCB7, GLRX5, STEAP3. -2 ALAS2 (known mutation R452C, P520L+possible new splicing mutation). -2 SLC25A38 NEW MUTATIONS. Publication Kannengiesser C*, Sanchez M*, Sweeney M* et al., . Haematologica. 2011 ).-19 non-sideroblastic Anemias => Seq. genes TF, CP, TMPRSS6, DMT1. -4 families TF (5 NEW MUTATIONS). Publication submitted BJH, Publication in preparation -4 families IRIDA (6 patients) 4 NEW MUTATIONS. Publication in preparation -IRIDA Review Publication Haematologica De Falco L*, Sánchez M*, et al. 2013 -1 new entity case NGS5 ongoing.- 15 CDAI/II => Seq. genes SEC23B, CDAN1, KLF1 -SEC23B: 4 NEW MUTATIONS (2 missense, 1 splicing, 1 insertion), 2 known mutations -CDAN1: 1 NEW missense MUTATIONTotal Cases 85, 101 affected patients, 155 studied persons (affected and non-affected)
    12. 12. Diagnóstico genético en nuevos casos de IRIDA(iron-refractory iron deficiency Anemia)
    13. 13. Gene TMPRSS6, Protein MATRIPTASE-2•Mask mouse. ENU mutagenesis mice. Inappropriate high hepcidinlevels. Positional cloning: TMPRSS6 gene (membrane-bound serineprotease), splicing error. (Dr. Beutler s lab. Science 2008).•TMPRSS6 KO mouse. Dr. Lopez-Otin s lab. Matriptase-2 is anessential regulator of iron homeostasis. Severe iron deficiency anemia. (Du et al., Science, 2008)(Folgueras et al., Blood 2008)•Human patients => IRIDA mutations in TMPRSS6 (Finberg KE et al. NatGenet. 2008; 40: 569-571)
    14. 14. IRIDA (OMIM #206200) • Anemia microcítica e hipocroma sin respuesta a hierro oral y respuesta parcial al hierro intravenoso • Infancia / adolescencia • Autosómico recesivo con baja prevalencia <1 / 1,000,000 (Orphanet) • Primer caso descrito en humanos en el 2008 (Finberg et al. 2008) • 44 pacientes reportados en 29 familias (14 publicaciones) • Mutaciones gen TMPRSS6, proteina Matriptase-2, serin proteasa membrane-bound. Regulador negativo de la hepcidina • Niveles de hepcidina inapropiadamente normales o altos (ELISA en la UDGAEMH)
    15. 15. IRIDA Kindreds. Clinical and Biochemical data We report 4 IRIDA families (6 patients) with 4 NEW mutations in TMPRSS6 Transferrin Serum Serum Patient Consan- RCB Hb MCV sat.Kindred Ancestry Sex Age 3 6 ferritin iron number guinity (mm x10 ) (gr/dL) (fl) (%) (ng/ml) (ug/dL) IV-1 Spain Yes M 14mo 4,38 6,8 50 5 170 13 A IV-2 (+) Spain Yes M 12mo 4,88 8,7 56,8 5 90 10 II-1 (+) Venezuela No M 7 years 4,79 10,5 67,7 12 132 36 B II-2 (+¤) Venezuela No F 1 year 5,29 10,3 61 6 367 26 C II-1 (+¤) Colombia No M 4 years 4,34 9,7 69 6 30 15 D II-1 (+¤) Spain No M 5 years 4,95 9,7 74 4 40 13 LOW LOW LOW LOW Clinical data reported at diagnosis: + Oral iron treatment ¤ Intravenous treatment
    16. 16. IRIDA Kindred A . New Nonsense mutation Lys StopNM_153609.2:c.[2252_2253insT];[2252_2253insT] Matriptase2 wt (811aa) 752 59NP_705837.1:p.(Lys752*);(Lys752*) Truncated Matriptase2 (752aa) 752
    17. 17. IRIDA Kindred B and C . New Missense mutation NM_153609.2:c.[861C>A];[861C>A] NP_705837.1:p.(Thr287Asn);(Thr287Asn) CONDEL: This variation is predicted to be a deleterious change (score =0.976 ).
    18. 18. IRIDA Kindred D. New Missense + frameshift mutationNM_153609.2:c.[76_81delGGTGA];[=] NM_153609.2:c.[1817T>C];[=]NP_705837.1:p.(Gly26Trpfs*14);(=) NP_705837.1:p.(Leu606Arg);(=) Leu606Arg CONDEL: This variation is predicted to be a deleterious change (score =0.902).
    19. 19. New mutations in IRIDA patients Mutation 1 Mutation 2 (NM_153609.2; (NM_153609.2; kindred Patient NP_705837.1) NP_705837.1) Domains c.2252_2253insT; c.2252_2253insT; IV-1 Protease/Protease p.Lys752* p.Lys752* A c.2252_2253insT; c.2252_2253insT; IV-2 Protease/Protease p.Lys752* p.Lys752* c.861C>A; c.861C>A; II-1 CUB I/CUB I p.Thr287Asn p.Thr287Asn B c.861C>A; c.861C>A; II-2 CUB I/CUB I p.Thr287Asn p.Thr287Asn c.861C>A; c.861C>A; C II-1 CUB I/CUB I p.Thr287Asn p.Thr287Asn c.76_81delGGTGA; c.1817 T>C]; D II-1 Transmembrane/Protease p.Gly26Trpfs*14 p. Leu606Arg
    20. 20. Conclusiones • Es altamente sugestivo que las variaciones encontradas en estas familias sean causantes de su clínica • Nuestros resultados extienden el patrón de mutaciones en el gen TMPRSS6 asociadas a IRIDA, confirmando la importancia de los análisis genéticos para el diagnóstico de la enfermedad • Es importante conocer los niveles de hepcidina (UDGAEMH)
    21. 21. Hereditary Hemochromatosis type III Functional characterization ofTransferrin Receptor 2 Gly792Arg mutation
    22. 22. Hereditary Hemochromatosis•Iron-overload genetic disease. Increased dietary iron absorption.•Hepatic iron accumulation. Hepatic cancer.•High sFerritin (>1000 ng/ml) + High Transferrin saturation (>80%)•Cirrosis, Hepatic cancer, Cardiomyopathy, Diabetes, Arthritis, Impotence,Hyperpigmentation, Hypogonadotropic hypogonadism Common Rare genetic disease Type HH 1 HH 3 HJ 2b HJ 2a HH 4 Classic HFE TFR2 Hemojuvelin Hepcidin Ferroportin (Chr 6p21.3) (Chr7q22) (Chr1p21) (Chr19q13.1) (Chr2q32)Onset adult juvenil adultHeredity Autosomal recessive Autosomal dominant
    23. 23. Type III Hereditary Hemochromatosis – TFR2 • Type III HH was first described in two Sicilian families by Clara Camaschella and collaborators in 2000 (Nat. Genetics) • TFR2 is a homologue of TFR1, type II transmembrene membrane protein expressed mostly in the liver and CD71+ early erythroids. • At least 50 families and 69 patients have been described with mutations in TFR2.
    24. 24. Case 23 and Case 7. Atypical HemochromatosisProband Case 23: Proband Case 7:- Woman. 57 years old - Woman. 27 years old- Diagnosed at 31 years old - Diagnosed at 23 years oldBiochemical and Clinical Symptoms: Biochemical and Clinical Symptoms:-Ferritin 1700-2200 ng/mL (normal value 200) -Ferritin 3944 ng/mL (Normal value 200)-Transferrin saturation high -Transferrin saturation 96% (normal value <45%)- Liver cirrhosis -Serum iron: 236 ug/dL- Massive deposits of iron (HII: 3,6) -Fibrosis- Hepatomegaly of 10 cm- Arthralgia in hands and knees. Treatment:- Amenorrhea -70 phlebotomies (14 g of iron removed)Treatment: -EPO>82 phlebotomies (16.3 g of iron removed)Relatives: Relatives: Father with hepatopathy, CH, VHC- Sister with DMI and hypersideremia- Grandmother dead because of hepatopaty Genetics:Genetics: -HFE :C282Y -/-; H63D +/+- HFE : C282Y -/-; H63D -/- - No mutations in HJV and HAMP- No mutations in HJV and HAMP
    25. 25. TFR2 Hemochromatosis. Gly792Arg mutation CASE 23 CASE 7 G792R G792R G792R +/- +/+ +/+ Control Control Mutated Mutated G G792R G792R AHomozygous Heterozygous
    26. 26. TFR2 Gly792Arg mutationVARIANT FOUND IN TRF2 GENErs 80338891: NM_003277: c.[2374 G>A]+[2374 G>A];NP_003218.2: p.Gly792Arg; G792R mutation was described in heterozygosity in a patient that carriers2 additional mutations (Lee and Barton, 2006)“The functional effect of TFR2 G792R is unknown, and in thecontext of the present patient, it is irrelevant” (because this patient carrierstwo other mutations R445Q and R396X in compound heterozygosity) First time G792R mutation is described in homozygosity (Case 23). What is the functional consequences of the G792R mutation?
    27. 27. Functional implication of TFR2 G792R mutation N-FLAG Cloning and Site directed mutagenesis Plasmid Hs. TFR2 cDNA Protein localization studies by immunofluorescence in HUH7 cells TFR2-C FLAG N FLAG-TFR2
    28. 28. Permeablized Cells C-Flag WILDTYPE TFR2 C-FLAG TFR2mut-G792R Anti-flag ONLY Anti-E-Cad ONLY DAPI ONLY MergedHUH7
    29. 29. Permeablized Cells N-Flag WILDTYPE TFR2 N-FLAG TFR2mut-G792R Anti-flag ONLY Anti-E-Cad ONLY DAPI ONLY MergedHUH7
    30. 30. NON-Permeablized Cells C-Flag WILDTYPE TFR2 C-FLAG TFR2mut-G792R Anti-flag ONLY Anti-E-Cad ONLY DAPI ONLY MergedHUH7
    31. 31. Bioinformatic studies of TFR2 G792R mutationrs 80338891: NM_003277: c.[2374 G>A];[2374 G>A]; NP_003218.2: p.Gly792Arg Structural analysis: TFR2 modelled based on TFR1Bioinformatic studies indicates: structure (PDB: 1DE4).1. Mutation is predicted as DELETERIOUS (SIFT) 1. G792R mutation is in a semi-buried location (relative /PROBABLY DAMAGING (Polyphen) accessibility 37.6%), at the inter-phase between2. G792 is 100% conserved between species TFR2 monomers.3. Glycine-Arginine change => large volume and => This is consistent with a dimer-disruptive impact of hydrophobicity change G792R.=> Destabilizing effect of G792R mutation on the structure/function of TFR2 monomer Collaboration: Dr Xavier de la Cruz and Dr Sergi Lois.
    32. 32. Conclusions• Genetic analysis of TFR2 revealed a previously described butuncharacterized change Gly792Arg in 2 Spanish families. Aputative splicing variation is also present in the proband ofCase 7 in heterozygous state.• First time this variation has been described in homozygosity(Case 23).• Co-IF analysis revealed that the TFR2 Gly792Arg mutatedprotein is unable to reach the cell membrane where its functionin iron metabolism takes place.•Bioinformatic and computational analysis on TFR2 Gly792Argmutation suggest that the mutation may destabilize both themonomer and the dimmer of TFR2, hence affecting itsfunctionality.
    33. 33. Proyecto hiperferritinemia
    34. 34. Agradecimientos•Iron and cancer group. Mayka Sanchez’s lab (IMPPC) • Dr. Ricky Joshi •Francisco Fuster•Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders Mayka Sanchez’s lab (IMPPC) • Dr. Erica Morán • Jessica Aranda•Dra. Bienvenida Argiles, Hospital de la Fe (Valencia, Spain)•Dra. Cristina Sanz, Hospital Clínic de Barcelona• Dr. Xavier de la Cruz and Dr. Sergio Lois (Vall de Hebrón, Spain)•Grupo Ibérico de Ferropatología (GIF) Research Projects and Contracts Ramón y Cajal Research Contract Technician Contrat (Carlos III) FIS (Health Ministery) – 2009-2012 European Project E-rare –2009-2012 Research Project: Ayuda a la Investigación Ramón Areces 2012-2015. Proyectos de Investigación Fundamental no Orientada - SAF 2012. Postdoctoral Fellowship FEBS 2012-2015
    35. 35. Gracias por vuestra atención! Jefe: Servicios • Dra. Mayka Sánchez Técnicos: - Hepcidina sérica/plasmática (ELISA) • Dr. Erica Morán • Jessica Aranda - Diagnóstico Genético enfermedades GIF raras del metabolismo del hierro Medical Doctors networkUnidad de Diagnóstico Genético Avanzado de Enfermedadesdel Metabolismo del Hierrro (UDGAEMH)http://www.imppc.org/resources-and-services/index.htmludgaemh@imppc.orgAcreditación de Calidad:EMQN EQA en HH-HFEDesignada como unidad EXPERTA por ORPHANETAcreditación asistencial Generalitat Catalunya
    36. 36. Gracias por vuestra atención! Mayka Sanchez CLINICAL GENETIC DIAGNOSTICS: Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders RESEARCH: Iron & CancerPostdocs Ricky Joshi, PhD Maya Shvarstman, PhDTechnicians Erica Morán, PhD Jessica ArandaPhD student Sara LuscietiBioinformatician Francisco Fuster
    37. 37. Propuesta- Estancias en la UDGAEMHEstamos interesados en formar a médicos especializados (especialmentehematólogos) en técnicas de . Oportunidad de colaborar y realizar estudios genéticos y funcionales enpacientes de nuestra unidad. Objetivo: aprender a trabajar en un laboratorio de diagnóstico genético, hacerinvestigación y publicar los datos en revistas internacionales. Financiación: nula ! (Así está la cosa... de mal…)Posibilidad de pedir contrato Rio Hortega y otros contratos dependiendo del Cv delcandidato.Interesados contactar con:Dra. Mayka Sanchez msanchez@imppc.orgPara más detalles sobre nosotros ver:http://www.imppc.org/research-activities/cancer-and-iron/http://www.imppc.org/resources-and-services/genetic-diagnostics-metabolism-disorders/
    38. 38. Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders PRICE CATEGORIES GENE DISEASE OMIM (euros) HFE HH1 120 235200 IRON Classical Hemochromatosis HAMP HH2 (juvenile form) 100 613313 OVERLOAD Non-HFE Hemochromatosis HFE2 HH2 (juvenile form) 100 602390 TFR2 HH3 200 604250 SLC40A1 HH4 160 606069 FTL Hereditary hyperferretinemia with cataracts 50 600886 HYPERFERRIT Hyperferritinemia FTL Benign Hyperferretinemia 100 600886 INEMIA FTH Hyperferretinemia with iron overload 100 134770 ALAS2 XLSA 150 300751 STEAP3 Sideroblastic anemia associated to STEAP3 150 609671 Sideroblastic ABCB7 XLSA with ataxia 100 301310 GLRX5 SA with hepatic iron overload 100 205950 SLC25A38 Non syndromic autosomal recessive CSA 100 205950 RARE IRON- CP Aceruloplasminemia 230 604290 RELATED TF Hypotransferrinemia 250 209300 ANEMIAS Non-sideroblastic Familiar microcytic hypochromic anemia SLC11A2 with hepatic iron overload 200 206100 TMPRSS6 IRIDA, Iron-refractory iron deficient anemia 200 206200 CDAN1 CDA type I 250 224120 Congenital SEC23B CDA type II 250 224100 dyserythropoietic anemia KLF1 Unclassified CDA 150 NA http://www.imppc.org/resources-and-services/index.html Dra. Mayka Sánchez. udgaemh@imppc.org
    39. 39. Gracias por vuestra atención!Advanced Genetic Diagnostic Unit for Rare Iron Metabolism Disorders Head: • Dr. Mayka Sánchez Technicians: • Dr. Erica Morán • Jessica Aranda GIF Medical Doctors networkhttp://www.imppc.org/resources-and-services/index.htmludgaemh@imppc.orgAcreditación de Calidad:EMQN EQA en HH-HFEDesignada como unidad EXPERTA por ORPHANETAcreditación asistencial Generalitat Catalunya

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