A valine deletion of ferroportin 1: a common mutation in hemochromatosis type 4?

Roetto, Antonella; Merryweather‐Clarke, Alison T.; Daraio, Filomena; Livesey, K; Pointon, Jennifer J.; Barbabietola, G; Piga, Antonio; Mackie, P H; Robson, Kathryn; Camaschella, Clara

doi:10.1182/blood-2002-03-0693

Cited by 96 publications

(56 citation statements)

References 11 publications

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“…The weh Th238 allele has a premature stop mutation and is thought to be a null allele (4). The weh Tp85c allele is of particular interest because it encodes a missense mutation (Leu 167 to Phe) in the same conserved region of fpn1 (4) as several of the missense mutations identified in patients with type 4 hemochromatosis (20)(21)(22)(23)(24)(25)(26). Both weh Tp85c and weh Th238 homozygotes develop severe anemia by 48 hours after fertilization and die between 10 and 14 days of age.…”

Section: Introductionmentioning

confidence: 99%

Ferroportin1 is required for normal iron cycling in zebrafish

Fraenkel¹,

Traver²,

Donovan³

et al. 2005

J. Clin. Invest.

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Missense mutations in ferroportin1 (fpn1), an intestinal and macrophage iron exporter, have been identified between transmembrane helices 3 and 4 in the zebrafish anemia mutant weissherbst (weh Tp85c -/-) and in patients with type 4 hemochromatosis. To explore the effects of fpn1 mutation on blood development and iron homeostasis in the adult zebrafish, weh Tp85c -/-zebrafish were rescued by injection with iron dextran and studied in comparison with injected and uninjected WT zebrafish and heterozygotes. Although iron deposition was observed in all iron-injected fish, only weh Tp85c -/-zebrafish exhibited iron accumulation in the intestinal epithelium compatible with a block in iron export. Iron injections initially reversed the anemia. However, 8 months after iron injections were discontinued, weh Tp85c -/-zebrafish developed hypochromic anemia and impaired erythroid maturation despite the persistence of iron-loaded macrophages and elevated hepatic nonheme iron stores. Quantitative real-time RT-PCR revealed a significant decrease in mean hepatic transcript levels of the secreted iron-regulator hepcidin and increased intestinal expression of fpn1 in anemic weh Tp85c -/-adults. Injection of iron dextran into WT or mutant zebrafish embryos, however, resulted in significant increases in hepcidin expression 18 hours after injection, demonstrating that hepcidin expression in zebrafish is iron responsive and independent of fpn1's function as an iron exporter.

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Section: Introductionmentioning

confidence: 99%

Ferroportin1 is required for normal iron cycling in zebrafish

Fraenkel¹,

Traver²,

Donovan³

et al. 2005

J. Clin. Invest.

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“…Hay que recordar que la ferroportina también se encuentra en la membrana basolateral de los enterocitos, en macrófagos, hepatocitos y placenta 53 . Mutaciones de la molécula se relacionan con la hemocromatosis hereditaria 54,55 . Los pacientes con este desorden poseen una absorción de Fe excesiva combinada con una disminución de la retención del mismo elemento en los macrófagos, lo que conduce a su acumulación parenquimal progresiva, con aparición de síntomas en la quinta década de la vida 56 .…”

Section: Ferroportina Y Hepcidinaunclassified

Proponiendo biomarcadores para evaluar las alteraciones en la homeostasis cerebral de hierro y su relación con la fisiopatología de la Enfermedad de Alzheimer

Tapia-Saavedra

2007

Rev. chil. neuro-psiquiatr.

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“…Since 2001, when the SLC40A1 gene was discovered, various mutations (N144H, A77D, Y64N, V162 del) have already been identified in the gene [49,83,84]. Thus, a loss-of-function mutation in the ferroportin 1 gene could cause an impairment of iron export from cells, mainly reticuloendothelial macrophages, with a consequent tissue iron accumulation (increase of serum ferritin) and a decreased availability of iron for circulating transferrin (low transferrin saturation), potentially responsible for a mild form of anemia.…”

Section: Type 4 Hereditary Hemochromatosis (Omim 606069)mentioning

confidence: 99%

Hereditary iron overload: Update on pathophysiology, diagnosis, and treatment

Franchini

2006

Am. J. Hematol.

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Hereditary hemochromatosis, a very common genetic defect in the Caucasian population, is characterized by progressive tissue iron overload which leads to irreversible organ damage if it is not treated timely. The elucidation of the molecular pathways of iron transport through cells and its control has led to the understanding of various genetic iron‐loading conditions. Four types of inherited iron overload have been recognized: type 1, the most common form with an autosomal recessive inheritance, is associated with mutations in the HFE gene on chromosome 6; type 2 (juvenile hemochromatosis) is an autosomal recessive disorder with causative mutations identified in the HJV gene (subtype A) on chromosome 1 and the HAMP gene (subtype B) on chromosome 19; type 3 has also an autosomal recessive inheritance with mutations in the TfR2 gene on chromosome 3; type 4 is an autosomal dominant condition with heterozygous mutations in the ferroportin 1 gene on chromosome 2. In this review, the genetics, pathophysiology, diagnosis, clinical features, and management of these different types of hereditary hemochromatosis are briefly discussed. Am. J. Hematol. 81:202–209, 2006. © 2006 Wiley‐Liss, Inc.

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A valine deletion of ferroportin 1: a common mutation in hemochromatosis type 4?

Cited by 96 publications

References 11 publications

Ferroportin1 is required for normal iron cycling in zebrafish

Ferroportin1 is required for normal iron cycling in zebrafish

Proponiendo biomarcadores para evaluar las alteraciones en la homeostasis cerebral de hierro y su relación con la fisiopatología de la Enfermedad de Alzheimer

Hereditary iron overload: Update on pathophysiology, diagnosis, and treatment

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